Tetraspanins and Cancer Metastasis

  • Margot Zöller
Part of the Cancer Drug Discovery and Development book series (CDD&D)


Metastasis formation is the final result of a cascade of events that primary tumor cells pass through by changing their phenotype and the crosstalk with the tumor environment. Molecules involved in this process are besides others tetraspanins, which surprisingly can either inhibit or promote metastasis formation. These opposing activities are supposed to rely on the special feature of tetraspanins that mostly act via modulating the activity of a multitude of associating molecules. Tetraspanins assemble a web between themselves and other associating molecules in special glycolipid-enriched membrane microdomains, which function as signaling platform, but are also prone for internalization. Internalization of tetraspanins and associated molecules by itself can contribute to promotion or inhibition of tumor progression. Notably, the internalized tetraspanin web is abundantly recovered in exosomes, small vesicles that derive from internalized membrane microdomains. Thus, it appears reasonable to assume that exosomal tetraspanins are of major importance for the crosstalk between the metastasizing tumor cell, the tumor stroma, the vessel endothelium, and the premetastatic organ. I will briefly introduce the structure of tetraspanins and their presently known main functional activities as a starting point to appreciate the contribution of selective tetraspanins in metastasis promotion and inhibition.


Epidermal Growth Factor Receptor Focal Adhesion Kinase Metastasis Formation Epidermal Growth Factor Receptor Activation Membrane Microdomains 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



This work was supported by the Deutsche Forschungsgemeinschaft (grant ZO 40/12-1), the Deutsche Krebshilfe, and the Tumorzentrum Heidelberg/Mannheim.


  1. Abache T, Le Naour F, Planchon S et al (2007) The transferrin receptor and the tetraspanin web molecules CD9, CD81, and CD9P-1 are differentially sorted into exosomes after TPA treatment of K562 cells. J Cell Biochem 102:650–664PubMedGoogle Scholar
  2. Adachi M, Taki T, Ieki Y et al (1996) Correlation of KAI1/CD82 gene expression with good prognosis in patients with non-small cell lung cancer. Cancer Res 56:1751–1755PubMedGoogle Scholar
  3. Adachi M, Taki T, Huang C et al (1998) Reduced integrin alpha3 expression as a factor of poor prognosis of patients with adenocarcinoma of the lung. J Clin Oncol 16:1060–1067PubMedGoogle Scholar
  4. Admyre C, Johansson SM, Paulie S et al (2006) Direct exosome stimulation of peripheral human T cells detected by ELISPOT. Eur J Immunol 36:1772–1781PubMedGoogle Scholar
  5. Aharon A, Brenner B (2009) Microparticles, thrombosis and cancer. Best Pract Res Clin Haematol 22:61–69PubMedGoogle Scholar
  6. Ahmad A, Hart IR (1997) Mechanisms of metastasis. Crit Rev Oncol Hematol 26:163–173PubMedGoogle Scholar
  7. Albini A, Mirisola V, Pfeffer U (2008) Metastasis signatures: genes regulating tumor-microenvironment interactions predict metastatic behavior. Cancer Metastasis Rev 27:75–83PubMedGoogle Scholar
  8. Al-Nedawi K, Meehan B, Rak J (2009) Microvesicles: messengers and mediators of tumor progression. Cell Cycle 8:2014–2018PubMedGoogle Scholar
  9. André F, Schartz NE, Chaput N et al (2002) Tumor-derived exosomes: a new source of tumor rejection antigens. Vaccine 20 Suppl 4:A28–A31Google Scholar
  10. André M, Le Caer JP, Greco C et al (2006) Proteomic analysis of the tetraspanin web using LC-ESI-MS/MS and MALDI-FTICR-MS. Proteomics 6:1437–1449PubMedGoogle Scholar
  11. Ang J, Lijovic M, Ashman LK et al (2004) CD151 protein expression predicts the clinical outcome of low-grade primary prostate cancer better than histologic grading: a new prognostic indicator? Cancer Epidemiol Biomarkers Prev 13:1717–1721PubMedGoogle Scholar
  12. Ardón-Alonso M, Yañez-Mó M, Barreiro O et al (2006) Tetraspanins CD9 and CD81 modulate HIV-1-induced membrane fusion. J Immunol 177:5129–5137Google Scholar
  13. Arduise C, Abache T, Li L et al (2008) Tetraspanins regulate ADAM10-mediated cleavage of TNF-alpha and epidermal growth factor. J Immunol 181:7002–7013PubMedGoogle Scholar
  14. Bahi A, Boyer F, Kolira M et al (2005) In vivo gene silencing of CD81 by lentiviral expression of small interference RNAs suppresses cocaine-induced behaviour. J Neurochem 92:1243–1255PubMedGoogle Scholar
  15. Baldwin G, Novitskaya V, Sadej R et al (2008) Tetraspanin CD151 regulates glycosylation of (alpha)3(beta)1 integrin. J Biol Chem 283:35445–35454PubMedGoogle Scholar
  16. Bandyopadhyay S, Zhan R, Chaudhuri A et al (2006) Interaction of KAI1 on tumor cells with DARC on vascular endothelium leads to metastasis suppression. Nat Med 12:933–938PubMedGoogle Scholar
  17. Bari R, Zhang YH, Zhang F et al (2009) Transmembrane interactions are needed for KAI1/CD82-mediated suppression of cancer invasion and metastasis. Am J Pathol 174:647–660PubMedGoogle Scholar
  18. Barreiro O, Yáñez-Mó M, Sala-Valdés M et al (2005) Endothelial tetraspanin microdomains regulate leukocyte firm adhesion during extravasation. Blood 105:2852–2861PubMedGoogle Scholar
  19. Bass R, Werner F, Odintsova E et al (2005) Regulation of urokinase receptor proteolytic function by the tetraspanin CD82. J Biol Chem 280:14811–14818PubMedGoogle Scholar
  20. Belting M, Wittrup A (2008) J Nanotubes, exosomes, and nucleic acid-binding peptides provide novel mechanisms of intercellular communication in eukaryotic cells: implications in health and disease. Cell Biol 183:1187–1191Google Scholar
  21. Berckmans RJ, Neiuwland R, Böing AN et al (2001) Cell-derived microparticles circulate in healthy humans and support low grade thrombin generation. Thromb Haemost 85:639–646PubMedGoogle Scholar
  22. Berditchevski F (2001) Complexes of tetraspanins with integrins: more than meets the eye. J Cell Sci 114:4143–4151PubMedGoogle Scholar
  23. Berditchevski F, Odintsova E (2007) Tetraspanins as regulators of protein trafficking. Traffic 8:89–96PubMedGoogle Scholar
  24. Berditchevski F, Bazzoni G, Hemler ME (1995) Specific association of CD63 with the VLA-3 and VLA-6 integrins. J Biol Chem 270:17784–17790PubMedGoogle Scholar
  25. Berditchevski F, Tolias KF, Wong K et al (1997) A novel link between integrins, transmembrane-4 superfamily proteins (CD63 and CD81), and phosphatidylinositol 4-kinase. J Biol Chem 272:2595–2598PubMedGoogle Scholar
  26. Berditchevski F, Odintsova E, Sawada S et al (2002) Expression of the palmitoylation-deficient CD151 weakens the association of alpha 3 beta 1 integrin with the tetraspanin-enriched microdomains and affects integrin-dependent signaling. J Biol Chem 277:36991–37000PubMedGoogle Scholar
  27. Bérubé NG, Speevak MD, Chevrette M (1994) Suppression of tumorigenicity of human prostate cancer cells by introduction of human chromosome del(12)(q13). Cancer Res 54:3077–3081PubMedGoogle Scholar
  28. Bienstock RJ, Barrett JC (2001) KAI1, a prostate metastasis suppressor: prediction of solvated structure and interactions with binding partners; integrins, cadherins, and cell-surface receptor proteins. Mol Carcinog 32:139–153PubMedGoogle Scholar
  29. Bijlmakers MJ, Marsh M (2003) The on-off story of protein palmitoylation. Trends Cell Biol 13:32–42PubMedGoogle Scholar
  30. Birchmeier C, Birchmeier W, Gherardi E et al (2003) Met, metastasis, motility and more. Nat Rev Mol Cell Biol 4:915–925PubMedGoogle Scholar
  31. Bissell MJ, Labarge MA (2005) Context, tissue plasticity, and cancer: are tumor stem cells also regulated by the microenvironment? Cancer Cell 7:17–23PubMedGoogle Scholar
  32. Boismenu R, Rhein M, Fischer WH et al (1996) A role for CD81 in early T cell development. Science 271:198–200PubMedGoogle Scholar
  33. Boucheix C, Rubinstein E (2001) Tetraspanins. Cell Mol Life Sci 58:1189–1205PubMedGoogle Scholar
  34. Boukerche H, Su ZZ, Emdad L et al (2005) mda-9/Syntenin: a positive regulator of melanoma metastasis. Cancer Res 65:10901–10911PubMedGoogle Scholar
  35. Brabletz T, Jung A, Spaderna S et al (2005) Opinion: migrating cancer stem cells – an integrated concept of malignant tumour progression. Nat Rev Cancer 5:744–749PubMedGoogle Scholar
  36. Bredel M, Bredel C, Juric D et al (2005) Functional network analysis reveals extended gliomagenesis pathway maps and three novel MYC-interacting genes in human gliomas. Cancer Res 65:8679–8689PubMedGoogle Scholar
  37. Briese J, Schulte HM, Sajin M et al (2008) Correlations between reduced expression of the metastasis suppressor gene KAI-1 and accumulation of p53 in uterine carcinomas and sarcomas. Virchows Arch 453:89–96PubMedGoogle Scholar
  38. Burghoff S, Ding Z, Gödecke S et al (2008) Horizontal gene transfer from human endothelial cells to rat cardiomyocytes after intracoronary transplantation. Cardiovasc Res 77:534–543PubMedGoogle Scholar
  39. Cannon KS, Cresswell P (2001) Quality control of transmembrane domain assembly in the tetraspanin CD82. EMBO J 20:2443–2453PubMedGoogle Scholar
  40. Caswell P, Norman J (2008) Endocytic transport of integrins during cell migration and invasion. Trends Cell Biol 18:257–263PubMedGoogle Scholar
  41. Charrin S, Le Naour F, Oualid M et al (2001) The major CD9 and CD81 molecular partner. Identification and characterization of the complexes. J Biol Chem 276:14329–14337PubMedGoogle Scholar
  42. Charrin S, Manié S, Oualid M et al (2002) Differential stability of tetraspanin/tetraspanin interactions: role of palmitoylation. FEBS Lett 516:139–144PubMedGoogle Scholar
  43. Charrin S, Manié S, Thiele C et al (2003) A physical and functional link between cholesterol and tetraspanins. Eur J Immunol 33:2479–2489PubMedGoogle Scholar
  44. Chen Z, Mustafa T, Trojanowicz B et al (2004) CD82, and CD63 in thyroid cancer. Int J Mol Med 14:517–527PubMedGoogle Scholar
  45. Cherukuri A, Carter RH, Brooks S et al (2004) B cell signaling is regulated by induced palmitoylation of CD81. J Biol Chem 279:31973–31982PubMedGoogle Scholar
  46. Claas C, Herrmann K, Matzku S et al (1996) Developmentally regulated expression of metastasis-associated antigens in the rat. Cell Growth Differ 7:663–678PubMedGoogle Scholar
  47. Claas C, Seiter S, Claas A et al (1998) Association between the rat homologue of CO-029, a metastasis-associated tetraspanin molecule and consumption coagulopathy. J Cell Biol 141:267–280PubMedGoogle Scholar
  48. Claas C, Stipp CS, Hemler ME (2001) Evaluation of prototype transmembrane 4 superfamily protein complexes and their relation to lipid rafts. J Biol Chem 276:7974–7984PubMedGoogle Scholar
  49. Claas C, Wahl J, Orlicky DJ et al (2005) The tetraspanin D6.1A and its molecular partners on rat carcinoma cells. Biochem J 389:99–110PubMedGoogle Scholar
  50. Clark KL, Oelke A, Johnson ME et al (2004) CD81 associates with 14–3–3 in a redox-regulated palmitoylation-dependent manner. J Biol Chem 279:19401–19406PubMedGoogle Scholar
  51. Coombs GS, Covey TM, Virshup DM (2008) Wnt signaling in development, disease and translational medicine. Curr Drug Targets 9:513–531PubMedGoogle Scholar
  52. Craft JA, Marsh NA (2003) Increased generation of platelet-derived microparticles following percutaneous transluminal coronary angioplasty. Blood Coagul Fibrinolysis 14:719–728PubMedGoogle Scholar
  53. De Bruyne E, Andersen TL, De Raeve H et al (2006) Endothelial cell-driven regulation of CD9 or motility-related protein-1 expression in multiple myeloma cells within the murine 5T33MM model and myeloma patients. Leukemia 20:1870–1879PubMedGoogle Scholar
  54. De Cicco M (2004) The prothrombotic state in cancer: pathogenic mechanisms. Crit Rev Oncol Hematol 50:187–196PubMedGoogle Scholar
  55. Defilippi P, Di Stefano P, Cabodi S (2006) p130Cas: a versatile scaffold in signaling networks. Trends Cell Biol 16:257–263PubMedGoogle Scholar
  56. de Gassart A, Géminard C, Hoekstra D et al (2004) Exosome secretion: the art of reutilizing nonrecycled proteins? Traffic 5:896–903PubMedGoogle Scholar
  57. Denzer K, Kleijmeer MJ, Heijnen HF et al (2000) Exosome: from internal vesicle of the multivesicular body to intercellular signaling device. J Cell Sci 113:3365–3374PubMedGoogle Scholar
  58. de Parseval A, Lerner DL, Borrow P et al (1997) Blocking of feline immunodeficiency virus infection by a monoclonal antibody to CD9 is via inhibition of virus release rather than interference with receptor binding. J Virol 71:5742–5749PubMedGoogle Scholar
  59. Deregibus MC, Cantaluppi V, Calogero R et al (2007) Endothelial progenitor cell derived microvesicles activate an angiogenic program in endothelial cells by a horizontal transfer of mRNA. Blood 110:2440–2448PubMedGoogle Scholar
  60. Deryugina EI, Quigley JP (2006) Matrix metalloproteinases and tumor metastasis. Cancer Metastasis Rev 25:9–34PubMedGoogle Scholar
  61. Dev KK (2004) Making protein interactions druggable: targeting PDZ domains. Nat Rev Drug Discov 3:1047–1056PubMedGoogle Scholar
  62. Devaux PF, Morris R (2004) Transmembrane asymmetry and lateral domains in biological membranes. Traffic 5:241–246PubMedGoogle Scholar
  63. Dong JT, Lamb PW, Rinker-Schaeffer CW et al (1995) KAI1, a metastasis suppressor gene for prostate cancer on human chromosome 11p11.2. Science 268:884–886PubMedGoogle Scholar
  64. Dong LM, Potter JD, White E et al (2008) Genetic susceptibility to cancer: the role of polymorphisms in candidate genes. JAMA 299:2423–2436PubMedGoogle Scholar
  65. Drapkin R, Crum CP, Hecht JL (2004) Expression of candidate tumor markers in ovarian carcinoma and benign ovary: evidence for a link between epithelial phenotype and neoplasia. Hum Pathol 35:1014–1021PubMedGoogle Scholar
  66. Drucker L, Tohami T, Tartakover-Matalon S et al (2006) Promoter hypermethylation of tetraspanin members contributes to their silencing in myeloma cell lines. Carcinogenesis 27: 197–204PubMedGoogle Scholar
  67. Duffield A, Kamsteeg EJ, Brown AN et al (2003) The tetraspanin CD63 enhances the internalization of the H,K-ATPase beta-subunit. Proc Natl Acad Sci USA 100:15560–15565PubMedGoogle Scholar
  68. Eble JA, Haier J (2006) Integrins in cancer treatment. Curr Cancer Drug Targets 6:89–105PubMedGoogle Scholar
  69. Edwards DR, Handsley MM, Pennington CJ (2008) The ADAM metalloproteinases. Mol Aspects Med 29:258–289PubMedGoogle Scholar
  70. Erler JT, Bennewith KL, Cox TR et al (2009) Hypoxia-induced lysyl oxidase is a critical mediator of bone marrow cell recruitment to form the premetastatic niche. Cancer Cell 15:35–44PubMedGoogle Scholar
  71. Escola JM, Kleijmeer MJ, Stoorvogel W et al (1998) Selective enrichment of tetraspan proteins on the internal vesicles of multivesicular endosomes and on exosomes secreted by human B-lymphocytes. J Biol Chem 273:20121–20127PubMedGoogle Scholar
  72. Fan H, Derynck R (1999) Ectodomain shedding of TGF-alpha and other transmembrane proteins is induced by receptor tyrosine kinase activation and MAP kinase signaling cascades. EMBO J 18:6962–6972PubMedGoogle Scholar
  73. Fang Y, Wu N, Gan X et al (2007) Higher-order oligomerization targets plasma membrane proteins and HIV gag to exosomes. PLoS Biol 5:e158Google Scholar
  74. Farhadieh RD, Smee R, Ow K et al (2004) Down-regulation of KAI1/CD82 protein expression in oral cancer correlates with reduced disease free survival and overall patient survival. Cancer Lett 213:91–98PubMedGoogle Scholar
  75. Fevrier B, Raposo G (2004) Exosomes: endosomal-derived vesicles shipping extracellular messages. Curr Opin Cell Biol 16:415–421PubMedGoogle Scholar
  76. Fitter S, Tetaz TJ, Berndt MC et al (1995) Molecular cloning of cDNA encoding a novel platelet-endothelial cell tetra-span antigen, PETA-3. Blood 86:1348–1355PubMedGoogle Scholar
  77. Flaumenhaft R (2006) Formation and fate of platelet microparticles. Blood Cells Mol Dis 36:182–187PubMedGoogle Scholar
  78. Fomina AF, Deerinck TJ, Ellisman MH (2003) Regulation of membrane trafficking and subcellular organization of endocytic compartments revealed with FM1–43 in resting and activated human T cells. Exp Cell Res 291:150–166PubMedGoogle Scholar
  79. Fraley TS, Tran TC, Corgan AM et al (2003) Phosphoinositide binding inhibits alpha-actinin bundling activity. J Biol Chem 278:24039–24045PubMedGoogle Scholar
  80. Friedl P, Wolf K (2003) Tumour-cell invasion and migration: diversity and escape mechanisms. Nat Rev Cancer 3:362–374PubMedGoogle Scholar
  81. Funakoshi T, Tachibana I, Hoshida Y et al (2003) Expression of tetraspanins in human lung cancer cells: frequent downregulation of CD9 and its contribution to cell motility in small cell lung cancer. Oncogene 22:674–687PubMedGoogle Scholar
  82. Furuya M, Kato H, Nishimura N et al (2005) Down-regulation of CD9 in human ovarian carcinoma cell might contribute to peritoneal dissemination: morphologic alteration and reduced expression of beta1 integrin subsets. Cancer Res 65:2617–2625PubMedGoogle Scholar
  83. Fuss H, Dubitzky W, Downes CS et al (2008) SRC family kinases and receptors: analysis of three activation mechanisms by dynamic systems modeling. Biophys J 94:1995–2006PubMedGoogle Scholar
  84. Gao AC, Lou W, Dong JT et al (2003) Defining regulatory elements in the human KAI1 (CD 82) metastasis suppressor gene. Prostate 57:256–260PubMedGoogle Scholar
  85. Garcia E, Nikolic DS, Piguet V (2008a) HIV-1 replication in dendritic cells occurs through a tetraspanin-containing compartment enriched in AP-3. Traffic 9:200–214PubMedGoogle Scholar
  86. Garcia-España A, Chung PJ, Sarkar IN et al (2008) Appearance of new tetraspanin genes during vertebrate evolution. Genomics 91:326–334PubMedGoogle Scholar
  87. Gassmann P, Enns A, Haier J (2004) Role of tumor cell adhesion and migration in organ-specific metastasis formation. Onkologie 27:577–582PubMedGoogle Scholar
  88. Geary SM, Cambareri AC, Sincock PM et al (2001) Differential tissue expression of epitopes of the tetraspanin CD151 recognised by monoclonal antibodies. Tissue Antigens 58:141–153PubMedGoogle Scholar
  89. Gensert JM, Baranova OV, Weinstein DE et al (2007) CD81, a cell cycle regulator, is a novel target for histone deacetylase inhibition in glioma cells. Neurobiol Dis 26:671–680PubMedGoogle Scholar
  90. Gesierich S (2006) Das Tetraspanin CO-029/D6.1A in Membrankomplexen und Exosomen: Einfluss auf Tumorprogression und Angiogenese. Dissertation, University of Karlsruhe, GermanyGoogle Scholar
  91. Gesierich S, Paret C, Hildebrand D et al (2005) Colocalization of the tetraspanins, CO-029 and CD151, with integrins in human pancreatic adenocarcinoma: impact on cell motility. Clin Cancer Res 11:2840–2852PubMedGoogle Scholar
  92. Gesierich S, Berezovskiy I, Ryschich E et al (2006) Systemic induction of the angiogenesis switch by the tetraspanin D6.1A/CO-029. Cancer Res 66:7083–7094PubMedGoogle Scholar
  93. Gibbings DJ, Ciaudo C, Erhardt M et al (2009) Multivesicular bodies associate with components of miRNA effector complexes and modulate miRNA activity. Nat Cell Biol 11:1143–1149PubMedGoogle Scholar
  94. Goschnick MW, Lau LM, Wee JL et al (2006) Impaired “outside-in” integrin alphaIIbbeta3 signaling and thrombus stability in TSSC6-deficient mice. Blood 108:1911–1918PubMedGoogle Scholar
  95. Gruenberg J, Stenmark H (2004) The biogenesis of multivesicular endosomes. Nat Rev Mol Cell Biol 5:317–323PubMedGoogle Scholar
  96. Guo J, Wenk MR, Pellegrini L et al (2003) Phosphatidylinositol 4-kinase type IIalpha is responsible for the phosphatidylinositol 4-kinase activity associated with synaptic vesicles. Proc Natl Acad Sci USA 100:3995–4000PubMedGoogle Scholar
  97. Guo XZ, Xu JH, Liu MP et al (2005) KAI1 inhibits anchorage-dependent and -independent pancreatic cancer cell growth. Oncol Rep 14:59–63PubMedGoogle Scholar
  98. Hakomori SI (2010) Glycosynaptic microdomains controlling tumor cell phenotype through alteration of cell growth, adhesion, and motility. FEBS Lett 584:1901–1906PubMedGoogle Scholar
  99. Hammond C, Denzin LK, Pan M et al (1998) The tetraspan protein CD82 is a resident of MHC class II compartments where it associates with HLA-DR, -DM, and -DO molecules. J Immunol 161:3282–3291PubMedGoogle Scholar
  100. Hao S, Ye Z, Li F et al (2006) Epigenetic transfer of metastatic activity by uptake of highly metastatic B16 melanoma cell-released exosomes. Exp Oncol 28:126–131PubMedGoogle Scholar
  101. Hasegawa H, Watanabe H, Nomura T et al (1997) Molecular cloning and expression of mouse homologue of SFA-1/PETA-3 (CD151), a member of the transmembrane 4 superfamily. Biochim Biophys Acta 1353:125–130PubMedGoogle Scholar
  102. Hasegawa M, Furuya M, Kasuya Y et al (2007) CD151 dynamics in carcinoma-stroma interaction: integrin expression, adhesion strength and proteolytic activity. Lab Invest 87:882–892PubMedGoogle Scholar
  103. Hashida H, Takabayashi A, Tokuhara T et al (2003) Clinical significance of transmembrane 4 superfamily in colon cancer. Br J Cancer 89:158–167PubMedGoogle Scholar
  104. Hashimoto A, Tarner IH, Bohle RM et al (2007) Analysis of vascular gene expression in arthritic synovium by laser-mediated microdissection. Arthritis Rheum 56:1094–1105PubMedGoogle Scholar
  105. He B, Liu L, Cook GA et al (2005) Tetraspanin CD82 attenuates cellular morphogenesis through down-regulating integrin alpha6-mediated cell adhesion. J Biol Chem 280:3346–3354PubMedGoogle Scholar
  106. Helle F, Dubuisson J (2008) Hepatitis C virus entry into host cells. Cell Mol Life Sci 65:100–112PubMedGoogle Scholar
  107. Hemler ME (2001) Specific tetraspanin functions. J Cell Biol 155:1103–1107PubMedGoogle Scholar
  108. Hemler ME (2003) Tetraspanin proteins mediate cellular penetration, invasion, and fusion events and define a novel type of membrane microdomain. Annu Rev Cell Dev Biol 19:397–422PubMedGoogle Scholar
  109. Hemler ME (2005) Tetraspanin functions and associated microdomains. Nat Rev Mol Cell Biol 6:801–811PubMedGoogle Scholar
  110. Hemler ME (2008) Targeting of tetraspanin proteins – potential benefits and strategies. Nat Rev Drug Discov 7:747–758PubMedGoogle Scholar
  111. Hemler ME, Mannion BA, Berditchevski F (1996) Association of TM4SF proteins with integrins: relevance to cancer. Biochim Biophys Acta 1287:67–71PubMedGoogle Scholar
  112. Herlevsen M, Schmidt DS, Miyazaki K et al (2003) The association of the tetraspanin D6.1A with the alpha6beta4 integrin supports cell motility and liver metastasis formation. J Cell Sci 116:4373–4390PubMedGoogle Scholar
  113. Herrlich A, Klinman E, Fu J et al (2008) Ectodomain cleavage of the EGF ligands HB-EGF, neuregulin1-{beta}, and TGF-{alpha} is specifically triggered by different stimuli and involves different PKC isoenzymes. FASEB J 22:4281–4295PubMedGoogle Scholar
  114. Higashiyama M, Taki T, Ieki Y et al (1995) Reduced motility related protein-1 (MRP-1/CD9) gene expression as a factor of poor prognosis in non-small cell lung cancer. Cancer Res 55:6040–6044PubMedGoogle Scholar
  115. Higashiyama M, Doi O, Kodama K et al (1997) Immunohistochemically detected expression of motility-related protein-1 (MRP-1/CD9) in lung adenocarcinoma and its relation to prognosis. Int J Cancer 74:205–211PubMedGoogle Scholar
  116. Hirst J, Bright NA, Rous B et al (1999) Characterization of a fourth adaptor-related protein complex. Mol Biol Cell 10:2787–2802PubMedGoogle Scholar
  117. Hlubek F, Spaderna S, Schmalhofer O et al (2007) Wnt/FZD signaling and colorectal cancer morphogenesis. Front Biosci 12:458–470PubMedGoogle Scholar
  118. Hong IK, Kim YM, Jeoung DI et al (2005) Tetraspanin CD9 induces MMP-2 expression by activating p38 MAPK, JNK and c-Jun pathways in human melanoma cells. Exp Mol Med 37:230–239PubMedGoogle Scholar
  119. Hong IK, Jin YJ, Byun HJ et al (2006) Homophilic interactions of Tetraspanin CD151 up-regulate motility and matrix metalloproteinase-9 expression of human melanoma cells through adhesion-dependent c-Jun activation signaling pathways. J Biol Chem 281:24279–24292PubMedGoogle Scholar
  120. Horejsí V, Vlcek C (1991) Novel structurally distinct family of leucocyte surface glycoproteins including CD9, CD37, CD53 and CD63. FEBS Lett 288:1–4PubMedGoogle Scholar
  121. Hori H, Yano S, Koufuji K et al (2004) CD9 expression in gastric cancer and its significance. J Surg Res 117:208–215PubMedGoogle Scholar
  122. Horváth G, Serru V, Clay D et al (1998) CD19 is linked to the integrin-associated tetraspans CD9, CD81, and CD82. J Biol Chem 273:30537–30543PubMedGoogle Scholar
  123. Hotta H, Ross AH, Huebner K et al (1998) Molecular cloning and characterization of an antigen associated with early stages of melanoma tumor progression. Cancer Res 48:2955–2962Google Scholar
  124. Houle CD, Ding XY, Foley JF et al (2002) Loss of expression and altered localization of KAI1 and CD9 protein are associated with epithelial ovarian cancer progression. Gynecol Oncol 86:69–78PubMedGoogle Scholar
  125. Huang CI, Kohno N, Ogawa E et al (1998) Correlation of reduction in MRP-1/CD9 and KAI1/CD82 expression with recurrences in breast cancer patients. Am J Pathol 153:973–983PubMedGoogle Scholar
  126. Huang CL, Liu D, Masuya D et al (2004) MRP-1/CD9 gene transduction downregulates Wnt signal pathways. Oncogene 23:7475–7483PubMedGoogle Scholar
  127. Huang H, Groth J, Sossey-Alaoui K et al (2005) Aberrant expression of novel and previously described cell membrane markers in human breast cancer cell lines and tumors. Clin Cancer Res 11:4357–4364PubMedGoogle Scholar
  128. Huang CL, Ueno M, Liu D et al (2006) MRP-1/CD9 gene transduction regulates the actin cytoskeleton through the downregulation of WAVE2. Oncogene 25:6480–6488PubMedGoogle Scholar
  129. Huang H, Sossey-Alaoui K, Beachy SH et al (2007) The tetraspanin superfamily member NET-6 is a new tumor suppressor gene. J Cancer Res Clin Oncol 133:761–769PubMedGoogle Scholar
  130. Huerta S, Harris DM, Jazirehi A et al (2003) Gene expression profile of metastatic colon cancer cells resistant to cisplatin-induced apoptosis. Int J Oncol 22:663–670PubMedGoogle Scholar
  131. Hurley JH, Emr SD (2006) The ESCRT complexes: structure and mechanism of a membrane-trafficking network. Annu Rev Biophys Biomol Struct 35:277–298PubMedGoogle Scholar
  132. Ichikawa T, Ichikawa Y, Isaacs JT (1991) Genetic factors and suppression of metastatic ability of prostatic cancer. Cancer Res 51:3788–3792PubMedGoogle Scholar
  133. Iero M, Valenti R, Huber V et al (2008) Tumour-released exosomes and their implications in cancer immunity. Cell Death Differ 15:80–88PubMedGoogle Scholar
  134. Ikeyama S, Koyama M, Yamaoko M et al (1993) Suppression of cell motility and metastasis by transfection with human motility-related protein (MRP-1/CD9) DNA. J Exp Med 177:1231–1237PubMedGoogle Scholar
  135. Imai T, Yoshie O (1993) C33 antigen and M38 antigen recognized by monoclonal antibodies inhibitory to syncytium formation by human T cell leukemia virus type 1 are both members of the transmembrane 4 superfamily and associate with each other and with CD4 or CD8 in T cells. J Immunol 151:6470–6481PubMedGoogle Scholar
  136. Imhof I, Gasper WJ, Derynck R (2008) Association of tetraspanin CD9 with transmembrane TGF{alpha} confers alterations in cell-surface presentation of TGF{alpha} and cytoskeletal organization. J Cell Sci 121:2265–2274PubMedGoogle Scholar
  137. Inoue G, Horiike N, Michitaka K et al (2001) The CD81 expression in liver in hepatocellular carcinoma. Int J Mol Med 7:67–71PubMedGoogle Scholar
  138. Ishitani T, Kishida S, Hyodo-Miura J et al (2003) The TAK1-NLK mitogen-activated protein kinase cascade functions in the Wnt-5a/Ca(2+) pathway to antagonize Wnt/beta-catenin ­signaling. Mol Cell Biol 23:131–139PubMedGoogle Scholar
  139. Israels SJ, McMillan-Ward EM (2005) CD63 modulates spreading and tyrosine phosphorylation of platelets on immobilized fibrinogen. Thromb Haemost 93:311–318PubMedGoogle Scholar
  140. Jackson P, Millar D, Kingsley E et al (2000) Methylation of a CpG island within the promoter region of the KAI1 metastasis suppressor gene is not responsible for down-regulation of KAI1 expression in invasive cancers or cancer cell lines. Cancer Lett 157:169–176PubMedGoogle Scholar
  141. Jackson P, Marreiros A, Russell PJ (2005) KAI1 tetraspanin and metastasis suppressor. Int J Biochem Cell Biol 37:530–534PubMedGoogle Scholar
  142. Jackson P, Rowe A, Grimm MO (2007) An alternatively spliced KAI1 mRNA is expressed at low levels in human bladder cancers and bladder cancer cell lines and is not associated with invasive behaviour. Oncol Rep 18:1357–1363PubMedGoogle Scholar
  143. Jang HI, Lee H (2003) A decrease in the expression of CD63 tetraspanin protein elevates invasive potential of human melanoma cells. Exp Mol Med 35:317–323PubMedGoogle Scholar
  144. Janmey PA, Lindberg U (2004) Cytoskeletal regulation: rich in lipids. Nat Rev Mol Cell Biol 5:658–666PubMedGoogle Scholar
  145. Janowska-Wieczorek A, Wysoczynski M, Kijowski J et al (2005) Microvesicles derived from activated platelets induce metastasis and angiogenesis in lung cancer. Int J Cancer 113: 752–760PubMedGoogle Scholar
  146. Janvier K, Bonifacino JS (2005) Role of the endocytic machinery in the sorting of lysosome-associated membrane proteins. Mol Biol Cell 16:4231–4242PubMedGoogle Scholar
  147. Johnson JL, Winterwood N, DeMali KA et al (2009) Tetraspanin CD151 regulates RhoA activation and the dynamic stability of carcinoma cell-cell contacts. J Cell Sci 122:2263–2273PubMedGoogle Scholar
  148. Johnstone RM (2006) Exosomes biological significance: A concise review. Blood Cells Mol Dis 36:315–321PubMedGoogle Scholar
  149. Jung KK, Liu XW, Chirco R et al (2006) Identification of CD63 as a tissue inhibitor of metalloproteinase-1 interacting cell surface protein. EMBO J 25:3934–3942PubMedGoogle Scholar
  150. Jung T, Castellana D, Klingbeil P et al (2009) CD44v6 dependence of premetastatic niche preparation by exosomes. Neoplasia 11:1093–1105PubMedGoogle Scholar
  151. Kaji K, Oda S, Shikano T et al (2000) The gamete fusion process is defective in eggs of Cd9-deficient mice. Nat Genet 24:279–282PubMedGoogle Scholar
  152. Kanetaka K, Sakamoto M, Yamamoto Y et al (2001) Overexpression of tetraspanin CO-029 in hepatocellular carcinoma. J Hepatol 35:637–642PubMedGoogle Scholar
  153. Kanetaka K, Sakamoto M, Yamamoto Y et al (2003) Possible involvement of tetraspanin CO-029 in hematogenous intrahepatic metastasis of liver cancer cells. J Gastroenterol Hepatol 18:1309–1314PubMedGoogle Scholar
  154. Kaplan RN, Riba RD, Zacharoulis S et al (2005) VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche. Nature 438:820–827PubMedGoogle Scholar
  155. Kaplan RN, Rafii S, Lyden D (2006) Preparing the “soil”: the premetastatic niche. Cancer Res 66:11089–11093PubMedGoogle Scholar
  156. Karamatic Crew V, Burton N, Kagan A et al (2004) CD151, the first member of the tetraspanin (TM4) superfamily detected on erythrocytes, is essential for the correct assembly of human basement membranes in kidney and skin. Blood 104:2217–2223PubMedGoogle Scholar
  157. Kawashima M, Doh-ura K, Mekada E et al (2002) CD9 expression in solid non-neuroepithelial tumors and infiltrative astrocytic tumors. J Histochem Cytochem 50:1195–1203PubMedGoogle Scholar
  158. Keller S, Sanderson MP, Stoeck A et al (2006) Exosomes: from biogenesis and secretion to biological function. Immunol Lett 107:102–108PubMedGoogle Scholar
  159. Kerbel R, Folkman J (2002) Clinical translation of angiogenesis inhibitors. Nat Rev Cancer 2:727–739PubMedGoogle Scholar
  160. Kessels H, Béguin S, Andree H et al (1994) Measurement of thrombin generation in whole blood – the effect of heparin and aspirin. Thromb Haemost 72:78–83PubMedGoogle Scholar
  161. Kim JH, Kim B, Cai L et al (2005) Transcriptional regulation of a metastasis suppressor gene by Tip60 and beta-catenin complexes. Nature 434:921–926PubMedGoogle Scholar
  162. Kitani S, Berenstein E, Mergenhagen S et al (1991) A cell surface glycoprotein of rat basophilic leukemia cells close to the high affinity IgE receptor (Fc epsilon RI). Similarity to human melanoma differentiation antigen ME491. J Biol Chem 266:1903–1909PubMedGoogle Scholar
  163. Kohno M, Hasegawa H, Miyake M et al (2002) CD151 enhances cell motility and metastasis of cancer cells in the presence of focal adhesion kinase. Int J Cancer 97:336–343PubMedGoogle Scholar
  164. Kolesnikova TV, Kazarov AR, Lemieux ME et al (2009) Glioblastoma inhibition by cell surface immunoglobulin protein EWI-2, in vitro and in vivo. Neoplasia 11:77–86PubMedGoogle Scholar
  165. Koo TH, Lee JJ, Kim EM et al (2002) Syntenin is overexpressed and promotes cell migration in metastatic human breast and gastric cancer cell lines. Oncogene 21:4080–4088PubMedGoogle Scholar
  166. Kovalenko OV, Yang X, Kolesnikova TV et al (2004) Evidence for specific tetraspanin homodimers: inhibition of palmitoylation makes cysteine residues available for cross-linking. Biochem J 377:407–417PubMedGoogle Scholar
  167. Kovalenko OV, Metcalf DG, DeGrado WF et al (2005) Structural organization and interactions of transmembrane domains in tetraspanin proteins. BMC Struct Biol 5:11PubMedGoogle Scholar
  168. Kovalenko OV, Yang XH, Hemler ME (2007) A novel cysteine cross-linking method reveals a direct association between claudin-1 and tetraspanin CD9. Mol Cell Proteomics 6:1855–1867PubMedGoogle Scholar
  169. Kuhn S, Koch M, Nübel T et al (2007) A complex of EpCAM, claudin-7, CD44 variant isoforms, and tetraspanins promotes colorectal cancer progression. Mol Cancer Res 5:553–567PubMedGoogle Scholar
  170. Kusukawa J, Ryu F, Kameyama T et al (2001) Reduced expression of CD9 in oral squamous cell carcinoma: CD9 expression inversely related to high prevalence of lymph node metastasis. J Oral Pathol 30:73–79Google Scholar
  171. Kwon MS, Shin SH, Yim SH et al (2007) CD63 as a biomarker for predicting the clinical outcomes in adenocarcinoma of lung. Lung Cancer 57:46–53PubMedGoogle Scholar
  172. Ladwein M, Pape UF, Schmidt DS et al (2005) The cell-cell adhesion molecule EpCAM interacts directly with the tight junction protein claudin-7. Exp Cell Res 309:345–357PubMedGoogle Scholar
  173. Lagaudrière-Gesbert C, Lebel-Binay S, Wiertz E et al (1997) The tetraspanin protein CD82 associates with both free HLA class I heavy chain and heterodimeric beta 2-microglobulin complexes. J Immunol 158:2790–2797PubMedGoogle Scholar
  174. Lakkaraju A, Rodriguez-Boulan E (2008) Itinerant exosomes: emerging roles in cell and tissue polarity. Trends Cell Biol 18:199–209PubMedGoogle Scholar
  175. Lan RF, Liu ZX, Liu XC et al (2005) CD151 promotes neovascularization and improves blood perfusion in a rat hind-limb ischemia model. J Endovasc Ther 12:469–478PubMedGoogle Scholar
  176. Latysheva N, Muratov G, Rajesh S et al (2006) Syntenin-1 is a new component of tetraspanin-enriched microdomains: mechanisms and consequences of the interaction of syntenin-1 with CD63. Mol Cell Biol 26:7707–7718PubMedGoogle Scholar
  177. Lau LM, Wee JL, Wright MD et al (2004) The tetraspanin superfamily member CD151 regulates outside-in integrin alphaIIbbeta3 signaling and platelet function. Blood 104:2368–2375PubMedGoogle Scholar
  178. Lazo PA (2007) Functional implications of tetraspanin proteins in cancer biology. Cancer Sci 98:1666–1677PubMedGoogle Scholar
  179. Leavey PJ, Timmons C, Frawley W et al (2006) KAI-1 expression in pediatric high-grade osteosarcoma. Pediatr Dev Pathol 9:219–224PubMedGoogle Scholar
  180. Lee JH, Seo YW, Park SR et al (2003) Expression of a splice variant of KAI1, a tumor metastasis suppressor gene, influences tumor invasion and progression. Cancer Res 63:7247–7255PubMedGoogle Scholar
  181. Lee JH, Park SR, Chay KO et al (2004) KAI1 COOH-terminal interacting tetraspanin (KITENIN), a member of the tetraspanin family, interacts with KAI1, a tumor metastasis suppressor, and enhances metastasis of cancer. Cancer Res 64:4235–4243PubMedGoogle Scholar
  182. Lekishvili T, Fromm E, Mujoomdar M et al (2008) The tumour-associated antigen L6 (L6-Ag) is recruited to the tetraspanin-enriched microdomains: implication for tumour cell motility. J Cell Sci 121:685–694PubMedGoogle Scholar
  183. Le Naour F, Zöller M (2008) The tumor antigen EpCAM: tetraspanins and the tight junction protein claudin-7, new partners, new functions. Front Biosci 13:5847–5865PubMedGoogle Scholar
  184. Le Naour F, André M, Boucheix C, Rubinstein E (2006) Membrane microdomains and proteomics: lessons from tetraspanin microdomains and comparison with lipid rafts. Proteomics 6:6447–6454PubMedGoogle Scholar
  185. Levy S, Shoham T (2005a) Protein-protein interactions in the tetraspanin web. Physiology (Bethesda) 20:218–224Google Scholar
  186. Levy S, Shoham T (2005b) The tetraspanin web modulates immune-signalling complexes. Nat Rev Immunol 5:136–148PubMedGoogle Scholar
  187. Levy S, Todd SC, Maecker HT (1998) CD81 (TAPA-1): a molecule involved in signal transduction and cell adhesion in the immune system. Annu Rev Immunol 16:89–109PubMedGoogle Scholar
  188. Lewis TB, Robison JE, Bastien R et al (2005) Molecular classification of melanoma using real-time quantitative reverse transcriptase-polymerase chain reaction. Cancer 104:1678–1686PubMedGoogle Scholar
  189. Li Q, Li L, Shi W et al (2006) Mechanism of action differences in the antitumor effects of transmembrane and secretory tumor necrosis factor-alpha in vitro and in vivo. Cancer Immunol Immunother 55:1470–1479PubMedGoogle Scholar
  190. Linder ME, Deschenes RJ (2007) Palmitoylation: policing protein stability and traffic. Nat Rev Mol Cell Biol 8:74–84PubMedGoogle Scholar
  191. Lishner M, Zismanov V, Tohami T et al (2008) Tetraspanins affect myeloma cell fate via Akt signaling and FoxO activation. Cell Signal 20:2309–2316PubMedGoogle Scholar
  192. Little KD, Hemler ME, Stipp CS (2004) Dynamic regulation of a GPCR-tetraspanin-G protein complex on intact cells: central role of CD81 in facilitating GPR56-Galpha q/11 association. Mol Biol Cell 15:2375–2387PubMedGoogle Scholar
  193. Liu WM, Zhang XA (2006) KAI1/CD82, a tumor metastasis suppressor. Cancer Lett 240:183–194PubMedGoogle Scholar
  194. Liu FS, Dong JT, Chen JT et al (2000) Frequent down-regulation and lack of mutation of the KAI1 metastasis suppressor gene in epithelial ovarian carcinoma. Gynecol Oncol 78:10–15PubMedGoogle Scholar
  195. Liu L, He B, Liu WM et al (2007) Tetraspanin CD151 promotes cell migration by regulating integrin trafficking. J Biol Chem 282:31631–31642PubMedGoogle Scholar
  196. Loewen CJ, Moritz OL, Tam BM et al (2003) The role of subunit assembly in peripherin-2 targeting to rod photoreceptor disk membranes and retinitis pigmentosa. Mol Biol Cell 14:3400–3413PubMedGoogle Scholar
  197. Lombardi DP, Geradts J, Foley JF et al (1999) Loss of KAI1 expression in the progression of colorectal cancer. Cancer Res 59:5724–5731PubMedGoogle Scholar
  198. Longo N, Yáñez-Mó M, Mittelbrunn M et al (2001) Regulatory role of tetraspanin CD9 in tumor-endothelial cell interaction during transendothelial invasion of melanoma cells. Blood 98:3717–3726PubMedGoogle Scholar
  199. Maecker HT, Todd SC, Levy S (1997) The tetraspanin superfamily: molecular facilitators. FASEB J 11:428–442PubMedGoogle Scholar
  200. Malik FA, Sanders AJ, Jiang WG (2009) KAI-1/CD82, the molecule and clinical implication in cancer and cancer metastasis. Histol Histopathol 24:519–530PubMedGoogle Scholar
  201. Malinda KM (2009) In vivo matrigel migration and angiogenesis assay. Methods Mol Biol 467:287–294PubMedGoogle Scholar
  202. Mannion BA, Berditchevski F, Kraeft SK et al (1996) Transmembrane-4 superfamily proteins CD81 (TAPA-1), CD82, CD63, and CD53 specifically associated with integrin alpha 4 beta 1 (CD49d/CD29). J Immunol 157:2039–2047PubMedGoogle Scholar
  203. Marhaba R, Zöller M (2004) CD44 in cancer progression: adhesion, migration and growth regulation. J Mol Histol 35:211–231PubMedGoogle Scholar
  204. Marken JS, Schieven GL, Hellström I et al (1992) Cloning and expression of the tumor-associated antigen L6. Proc Natl Acad Sci USA 89:3503–3507PubMedGoogle Scholar
  205. Marks MS, Ohno H, Kirchnausen T et al (1997) Protein sorting by tyrosine-based signals: adapting to the Ys and wherefores. Trends Cell Biol 7:124–128PubMedGoogle Scholar
  206. Marreiros A, Czolij R, Yardley G et al (2003) Identification of regulatory regions within the KAI1 promoter: a role for binding of AP1, AP2 and p53. Gene 302:155–164PubMedGoogle Scholar
  207. Marreiros A, Dudgeon K, Dao V et al (2005) KAI1 promoter activity is dependent on p53, junB and AP2: evidence for a possible mechanism underlying loss of KAI1 expression in cancer cells. Oncogene 24:637–649PubMedGoogle Scholar
  208. Martin F, Roth DM, Jans DA et al (2005) Tetraspanins in viral infections: a fundamental role in viral biology? J Virol 79:10839–10851PubMedGoogle Scholar
  209. Mathivanan S, Lim JW, Tauro BJ et al (2010) Proteomic analysis of A33-immunoaffinity-purified exosomes released from the human colon tumor cell line LIM1215 reveals a tissue-specific protein signature. Mol Cell Proteomics 9:197–208PubMedGoogle Scholar
  210. Matzku S, Wenzel A, Liu S et al (1989) Antigenic differences between metastatic and nonmetastatic BSp73 rat tumor variants characterized by monoclonal antibodies. Cancer Res 49:1294–1299PubMedGoogle Scholar
  211. Mazzocca A, Liotta F, Carloni V (2008) Tetraspanin CD81-regulated cell motility plays a critical role in intrahepatic metastasis of hepatocellular carcinoma. Gastroenterology 135: 244–256PubMedGoogle Scholar
  212. Mhawech P, Herrmann F, Coassin M et al (2003) Motility-related protein 1 (MRP-1/CD9) expression in urothelial bladder carcinoma and its relation to tumor recurrence and progression. Cancer 98:1649–1657PubMedGoogle Scholar
  213. Mhawech P, Dulguerov P, Tschanz E et al (2004) Motility-related protein-1 (MRP-1/CD9) expression can predict disease-free survival in patients with squamous cell carcinoma of the head and neck. Br J Cancer 90:471–475PubMedGoogle Scholar
  214. Mimori K, Kataoka A, Yoshinaga K et al (2005) Identification of molecular markers for metastasis-related genes in primary breast cancer cells. Clin Exp Metastasis 22:59–67PubMedGoogle Scholar
  215. Mitsuzuka K, Handa K, Satoh M et al (2005) A specific microdomain (“glycosynapse 3”) controls phenotypic conversion and reversion of bladder cancer cells through GM3-mediated interaction of alpha3beta1 integrin with CD9. J Biol Chem 280:35545–35553PubMedGoogle Scholar
  216. Miura Y, Kainuma M, Jiang H et al (2004) Reversion of the Jun-induced oncogenic phenotype by enhanced synthesis of sialosyllactosylceramide (GM3 ganglioside). Proc Natl Acad Sci USA 101:16204–16209PubMedGoogle Scholar
  217. Miyake M, Adachi M, Huang C et al (1999) A novel molecular staging protocol for non-small cell lung cancer. Oncogene 18:2397–2404PubMedGoogle Scholar
  218. Miyamoto S, Maruyama A, Okugawa K et al (2001) Loss of motility-related protein 1 (MRP1/CD9) and integrin alpha3 expression in endometrial cancers. Cancer 92:542–548PubMedGoogle Scholar
  219. Miyazaki T, Müller U, Campbell KS (1997) Normal development but differentially altered proliferative responses of lymphocytes in mice lacking CD81. EMBO J 16:4217–4225PubMedGoogle Scholar
  220. Miyazaki T, Kato H, Shitara Y et al (2000) Mutation and expression of the metastasis suppressor gene KAI1 in esophageal squamous cell carcinoma. Cancer 89:955–962PubMedGoogle Scholar
  221. Mohan A, Nalini V, Mallikarjuna K et al (2007) Expression of motility-related protein MRP1/CD9, N-cadherin, E-cadherin, alpha-catenin and beta-catenin in retinoblastoma. Exp Eye Res 84:781–789PubMedGoogle Scholar
  222. Molina S, Castet V, Pichard-Garcia L et al (2008) Serum-derived hepatitis C virus infection of primary human hepatocytes is tetraspanin CD81 dependent. J Virol 82:569–574PubMedGoogle Scholar
  223. Morel O, Hugel B, Jesel L et al (2004) Circulating procoagulant microparticles and soluble GPV in myocardial infarction treated by primary percutaneous transluminal coronary angioplasty. A possible role for GPIIb-IIIa antagonists. J Thromb Haemost 2:1118–1126PubMedGoogle Scholar
  224. Mori M, Mimori K, Shiraishi T et al (1998) Motility related protein 1 (MRP1/CD9) expression in colon cancer. Clin Cancer Res 4:1507–1510PubMedGoogle Scholar
  225. Moss ML, Bartsch JW (2004) Therapeutic benefits from targeting of ADAM family members. Biochemistry 43:7227–7235PubMedGoogle Scholar
  226. Mott JD, Werb Z (2004) Regulation of matrix biology by matrix metalloproteinases. Curr Opin Cell Biol 16:558–564PubMedGoogle Scholar
  227. Murayama Y, Miyagawa J, Oritani K et al (2004) CD9-mediated activation of the p46 Shc isoform leads to apoptosis in cancer cells. J Cell Sci 117:3379–3388PubMedGoogle Scholar
  228. Murayama Y, Shinomura Y, Oritani K et al (2008) The tetraspanin CD9 modulates epidermal growth factor receptor signaling in cancer cells. J Cell Physiol 216:135–143PubMedGoogle Scholar
  229. Nakamura K, Mitamura T, Takahashi T et al (2000) Importance of the major extracellular domain of CD9 and the epidermal growth factor (EGF)-like domain of heparin-binding EGF-like growth factor for up-regulation of binding and activity. J Biol Chem 275:18284–18290PubMedGoogle Scholar
  230. Nakatsu F, Ohno H (2003) Adaptor protein complexes as the key regulators of protein sorting in the post-Golgi network. Cell Struct Funct 28:419–429PubMedGoogle Scholar
  231. Nakazawa Y, Sato S, Naito M et al (2008) Tetraspanin family member CD9 inhibits Aggrus/podoplanin-induced platelet aggregation and suppresses pulmonary metastasis. Blood 112:1730–1739PubMedGoogle Scholar
  232. Nazarenko I, Rana S, Baumann A et al (2010) Cell surface tetraspanin Tspan8 contributes to molecular pathways of exosome-induced endothelial cell activation. Cancer Res 70:1668–1678PubMedGoogle Scholar
  233. Ng T, Shima D, Squire A et al (1999) PKCalpha regulates beta1 integrin-dependent cell motility through association and control of integrin traffic. EMBO J 18:3909–3923PubMedGoogle Scholar
  234. Nichols TC, Guthridge JM, Karp DR et al (1998) Gamma-glutamyl transpeptidase, an ecto-enzyme regulator of intracellular redox potential, is a component of TM4 signal transduction complexes. Eur J Immunol 28:4123–4129PubMedGoogle Scholar
  235. Nübel T, Preobraschenski J, Tuncay H et al (2009) Claudin-7 regulates EpCAM-mediated functions in tumor progression. Mol Cancer Res 7:285–299PubMedGoogle Scholar
  236. Odintsova E, Sugiura T, Berditchevski F (2000) Attenuation of EGF receptor signaling by a metastasis suppressor, the tetraspanin CD82/KAI-1. Curr Biol 10:1009–1012PubMedGoogle Scholar
  237. Odintsova E, Voortman J, Gilbert E et al (2003) Tetraspanin CD82 regulates compartmentalisation and ligand-induced dimerization of EGFR. J Cell Sci 116:4557–4566PubMedGoogle Scholar
  238. Odintsova E, Butters TD, Monti E et al (2006) Gangliosides play an important role in the organization of CD82-enriched microdomains. Biochem J 400:315–325PubMedGoogle Scholar
  239. Ono M, Handa K, Withers DA et al (1999) Motility inhibition and apoptosis are induced by metastasis-suppressing gene product CD82 and its analogue CD9, with concurrent glycosylation. Cancer Res 59:2335–2339PubMedGoogle Scholar
  240. Oren R, Takahashi S, Doss C et al (1990) TAPA-1, the target of an antiproliferative antibody, defines a new family of transmembrane proteins. Mol Cell Biol 10:4007–4015PubMedGoogle Scholar
  241. Ovalle S, Gutiérrez-López MD, Olmo N et al (2007) The tetraspanin CD9 inhibits the proliferation and tumorigenicity of human colon carcinoma cells. Int J Cancer 121:2140–2152PubMedGoogle Scholar
  242. Pan BT, Teng K, Wu C et al (1985) Electron microscopic evidence for externalization of the transferrin receptor in vesicular form in sheep reticulocytes. J Cell Biol 101:942–948PubMedGoogle Scholar
  243. Pap E, Pállinger E, Pásztói M, Falus A (2009) Highlights of a new type of intercellular communication: microvesicle-based information transfer. Inflamm Res 58:1–8PubMedGoogle Scholar
  244. Peer D, Park EJ, Morishita Y et al (2008) Systemic leukocyte-directed siRNA delivery revealing cyclin D1 as an anti-inflammatory target. Science 319:627–630PubMedGoogle Scholar
  245. Percherancier Y, Planchenault T, Valenzuela-Fernandez A et al (2001) Palmitoylation-dependent control of degradation, life span, and membrane expression of the CCR5 receptor. J Biol Chem 276:31936–31944PubMedGoogle Scholar
  246. Phillips KK, White AE, Hicks DJ et al (1998) Correlation between reduction of metastasis in the MDA-MB-435 model system and increased expression of the Kai-1 protein. Mol. Carcinog 21:111–120PubMedGoogle Scholar
  247. Pileri P, Uematsu Y, Campagnoli S et al (1998) Binding of hepatitis C virus to CD81. Science 282:938–941PubMedGoogle Scholar
  248. Pols MS, Klumperman J (2009) Trafficking and function of the tetraspanin CD63. Exp Cell Res 315:1584–1592PubMedGoogle Scholar
  249. Potolicchio I, Carven GJ, Xu X et al (2005) Proteomic analysis of microglia-derived exosomes: metabolic role of the aminopeptidase CD13 in neuropeptide catabolism. J Immunol 175:2237–2243PubMedGoogle Scholar
  250. Press OW, Eary JF, Badger CC et al (1989) Treatment of refractory non-Hodgkin’s lymphoma with radiolabeled MB-1 (anti-CD37) antibody. J Clin Oncol 7:1027–1038PubMedGoogle Scholar
  251. Prince S, Carreira S, Vance KW et al (2004) Tbx2 directly represses the expression of the p21(WAF1) cyclin-dependent kinase inhibitor. Cancer Res 64:1669–1674PubMedGoogle Scholar
  252. Protzel C, Kakies C, Kleist B et al (2008) Down-regulation of the metastasis suppressor protein KAI1/CD82 correlates with occurrence of metastasis, prognosis and presence of HPV DNA in human penile squamous cell carcinoma. Virchows Arch 452:369–375PubMedGoogle Scholar
  253. Radford KJ, Mallesch J, Hersey P (1995) Suppression of human melanoma cell growth and metastasis by the melanoma-associated antigen CD63 (ME491). Int J Cancer 62:631–635PubMedGoogle Scholar
  254. Radford KJ, Thorne RF, Hersey P (1996) CD63 associates with transmembrane 4 superfamily members, CD9 and CD81, and with beta 1 integrins in human melanoma. Biochem Biophys Res Commun 222:13–18PubMedGoogle Scholar
  255. Ratajczak J, Miekus K, Kucia M et al (2006) Embryonic stem cell-derived microvesicles reprogram hematopoietic progenitors: evidence for horizontal transfer of mRNA and protein delivery. Leukemia 20:847–856PubMedGoogle Scholar
  256. Razmara M, Hu H, Masquelier M et al (2007) Glycoprotein IIb/IIIa blockade inhibits platelet aminophospholipid exposure by potentiating translocase and attenuating scramblase activity. Cell Mol Life Sci 64:999–1008PubMedGoogle Scholar
  257. Ribatti D, Nico B, Crivellato E et al (2007) The history of the angiogenic switch concept. Leukemia 21:44–52PubMedGoogle Scholar
  258. Rocha-Perugini V, Lavie M, Delgrange D et al (2009) The association of CD81 with tetraspanin-enriched microdomains is not essential for Hepatitis C virus entry. BMC Microbiol 9:111PubMedGoogle Scholar
  259. Rous BA, Reaves BJ, Ihrke G et al (2002) Role of adaptor complex AP-3 in targeting wild-type and mutated CD63 to lysosomes. Mol Biol Cell 13:1071–1082PubMedGoogle Scholar
  260. Rowe A, Jackson P (2006) Expression of KITENIN, a KAI1/CD82 binding protein and metastasis enhancer, in bladder cancer cell lines: relationship to KAI1/CD82 levels and invasive behaviour. Oncol Rep 16:1267–1272PubMedGoogle Scholar
  261. Rubinstein E, Le Naour F, Lagaudrière-Gesbert C et al (1996) CD9, CD63, CD81, and CD82 are components of a surface tetraspan network connected to HLA-DR and VLA integrins. Eur J Immunol 26:2657–2665PubMedGoogle Scholar
  262. Rubinstein E, Ziyyat A, Wolf JP et al (2006) The molecular players of sperm-egg fusion in mammals. Semin Cell Dev Biol 17:254–263PubMedGoogle Scholar
  263. Sachs N, Kreft M, van den Bergh Weerman MA et al (2006) Kidney failure in mice lacking the tetraspanin CD151. J Cell Biol 175:33–39PubMedGoogle Scholar
  264. Saito Y, Tachibana I, Takeda Y et al (2006) Absence of CD9 enhances adhesion-dependent morphologic differentiation, survival, and matrix metalloproteinase-2 production in small cell lung cancer cells. Cancer Res 66:9557–9565PubMedGoogle Scholar
  265. Sala-Valdés M, Ursa A, Charrin S et al (2006) EWI-2 and EWI-F link the tetraspanin web to the actin cytoskeleton through their direct association with ezrin-radixin-moesin proteins. J Biol Chem 281:19665–19675PubMedGoogle Scholar
  266. Sauer G, Kurzeder C, Grundmann R et al (2003a) Expression of tetraspanin adaptor proteins below defined threshold values is associated with in vitro invasiveness of mammary carcinoma cells. Oncol Rep 10:405–410PubMedGoogle Scholar
  267. Sauer G, Windisch J, Kurzeder C et al (2003b) Progression of cervical carcinomas is associated with down-regulation of CD9 but strong local re-expression at sites of transendothelial invasion. Clin Cancer Res 9:6426–6431PubMedGoogle Scholar
  268. Sawada S, Yoshimoto M, Odintsova E et al (2003) The tetraspanin CD151 functions as a negative regulator in the adhesion-dependent activation of Ras. J Biol Chem 278:26323–26326PubMedGoogle Scholar
  269. Schindl M, Birner P, Bachtiary B et al (2000) The impact of expression of the metastasis suppressor protein KAI1 on prognosis in invasive squamous cell cervical cancer. Anticancer Res 20:4551–4555PubMedGoogle Scholar
  270. Schmidt DS, Klingbeil P, Schnölzer M et al (2004) CD44 variant isoforms associate with tetraspanins and EpCAM. Exp Cell Res 297:329–347PubMedGoogle Scholar
  271. Schöniger-Hekele M, Hänel S, Wrba F et al (2005) Hepatocellular carcinoma – survival and clinical characteristics in relation to various histologic molecular markers in Western patients. Liver Int 25:62–69PubMedGoogle Scholar
  272. Schorey JS, Bhatnagar S (2008) Exosome function: from tumor immunology to pathogen biology. Traffic 9:871–881PubMedGoogle Scholar
  273. Seigneuret M (2006) Complete predicted three-dimensional structure of the facilitator transmembrane protein and hepatitis C virus receptor CD81: conserved and variable structural domains in the tetraspanin superfamily. Biophys J 90:212–227PubMedGoogle Scholar
  274. Seigneuret M, Delaguillaumie A, Lagaudrière-Gesbert C et al (2001) Structure of the tetraspanin main extracellular domain. A partially conserved fold with a structurally variable domain insertion. J Biol Chem 276:40055–40064PubMedGoogle Scholar
  275. Sela BA, Steplewski Z, Koprowski H (1989) Colon carcinoma-associated glycoproteins recognized by monoclonal antibodies CO-029 and GA22–2. Hybridoma 8:481–491PubMedGoogle Scholar
  276. Seow Y, Wood MJ (2009) Biological gene delivery vehicles: beyond viral vectors. Mol Ther 17:767–777PubMedGoogle Scholar
  277. Serru V, Le Naour F, Billard M et al (1999) Selective tetraspan-integrin complexes (CD81/alpha4beta1, CD151/alpha3beta1, CD151/alpha6beta1) under conditions disrupting tetraspan interactions. Biochem J 340:103–111PubMedGoogle Scholar
  278. Sharma C, Yang XH, Hemler ME (2008) DHHC2 affects palmitoylation, stability, and functions of tetraspanins CD9 and CD151. Mol Biol Cell 19:3415–3425PubMedGoogle Scholar
  279. Shet AS, Aras O, Gupta K et al (2003) Sickle blood contains tissue factor-positive microparticles derived from endothelial cells and monocytes. Blood 102:2678–2683PubMedGoogle Scholar
  280. Shi W, Fan H, Shum L et al (2000) The tetraspanin CD9 associates with transmembrane TGF-alpha and regulates TGF-alpha-induced EGF receptor activation and cell proliferation. J Cell Biol 148:591–602PubMedGoogle Scholar
  281. Shinohara T, Nishimura N, Hanibuchi M et al (2001) Transduction of KAI1/CD82 cDNA promotes hematogenous spread of human lung-cancer cells in natural killer cell-depleted SCID mice. Int J Cancer 94:16–23PubMedGoogle Scholar
  282. Shiomi T, Inoki I, Kataoka F et al (2005) Pericellular activation of proMMP-7 (promatrilysin-1) through interaction with CD151. Lab Invest 85:1489–1506PubMedGoogle Scholar
  283. Sierko E, Wojtukiewicz MZ (2007) Inhibition of platelet function: does it offer a chance of better cancer progression control? Semin Thromb Hemost 33:712–721PubMedGoogle Scholar
  284. Sigala S, Faraoni I, Botticini D et al (1999) Suppression of telomerase, reexpression of KAI1, and abrogation of tumorigenicity by nerve growth factor in prostate cancer cell lines. Clin Cancer Res 5:1211–1218PubMedGoogle Scholar
  285. Silvie O, Rubinstein E, Franetich JF et al (2003) Hepatocyte CD81 is required for Plasmodium falciparum and Plasmodium yoelii sporozoite infectivity. Nat Med 9:93–96PubMedGoogle Scholar
  286. Simons M, Raposo G (2009) Exosomes – vesicular carriers for intercellular communication. Curr Opin Cell Biol 21:575–581PubMedGoogle Scholar
  287. Simpson RJ, Jensen SS, Lim JW (2008) Proteomic profiling of exosomes: current perspectives. Proteomics 8:4083–4099PubMedGoogle Scholar
  288. Simpson RJ, Lim JW, Moritz RL et al (2009) Exosomes: proteomic insights and diagnostic potential. Expert Rev Proteomics 6:267–283PubMedGoogle Scholar
  289. Sincock PM, Mayrhofer G, Ashman LK (1997) Localization of the transmembrane 4 superfamily (TM4SF) member PETA-3 (CD151) in normal human tissues: comparison with CD9, CD63, and alpha5beta1 integrin. J Histochem Cytochem 45:515–525PubMedGoogle Scholar
  290. Sincock PM, Fitter S, Parton RG et al (1999) PETA-3/CD151, a member of the transmembrane 4 superfamily, is localised to the plasma membrane and endocytic system of endothelial cells, associates with multiple integrins and modulates cell function. J Cell Sci 112:833–844PubMedGoogle Scholar
  291. Singethan K, Müller N, Schubert S et al (2008) CD9 clustering and formation of microvilli zippers between contacting cells regulates virus-induced cell fusion. Traffic 9:924–235PubMedGoogle Scholar
  292. Skubitz KM, Campbell KD, Iida J et al (1996) CD63 associates with tyrosine kinase activity and CD11/CD18, and transmits an activation signal in neutrophils. J Immunol 157:3617–3626PubMedGoogle Scholar
  293. Smalheiser NR (2007) Exosomal transfer of proteins and RNAs at synapses in the nervous system. Biol Direct 2:35PubMedGoogle Scholar
  294. Son BH, Choi JS, Lee JH (2005) Prognostic values of KAI1 and survivin expression in an infiltrating ductal carcinoma of the breast. Pathology 37:131–136PubMedGoogle Scholar
  295. Sood SL (2009) Cancer-associated thrombosis. Curr Opin Hematol 16:378–385PubMedGoogle Scholar
  296. Sordat I, Decraene C, Silvestre T et al (2002) Complementary DNA arrays identify CD63 tetraspanin and alpha3 integrin chain as differentially expressed in low and high metastatic human colon carcinoma cells. Lab Invest 82:1715–1724PubMedGoogle Scholar
  297. Spoden G, Freitag K, Husmann M et al (2008) Clathrin- and caveolin-independent entry of human papillomavirus type 16 – involvement of tetraspanin-enriched microdomains (TEMs). PLoS One 3:e3313PubMedGoogle Scholar
  298. Sridhar SC, Miranti CK (2006) Tetraspanin KAI1/CD82 suppresses invasion by inhibiting integrin-dependent crosstalk with c-Met receptor and Src kinases. Oncogene 25:2367–2378PubMedGoogle Scholar
  299. Stafford LJ, Vaidya KS, Welch DR (2008) Metastasis suppressors genes in cancer. Int J Biochem Cell Biol 40:874–891PubMedGoogle Scholar
  300. Staflin K, Zuchner T, Honeth G et al (2009) Identification of proteins involved in neural progenitor cell targeting of gliomas. BMC Cancer 9:206PubMedGoogle Scholar
  301. Stahl PD, Barbieri MA (2002) Multivesicular bodies and multivesicular endosomes: the “ins and outs” of endosomal traffic. Sci STKE 2002(141):PE32PubMedGoogle Scholar
  302. Steeg PS (2003) Metastasis suppressors alter the signal transduction of cancer cells. Nat Rev Cancer 3:55–63PubMedGoogle Scholar
  303. Sterk LM, Geuijen CA, Oomen LC et al (2000) The tetraspan molecule CD151, a novel constituent of hemidesmosomes, associates with the integrin alpha6beta4 and may regulate the spatial organization of hemidesmosomes. J Cell Biol 149:969–982PubMedGoogle Scholar
  304. Stipp CS, Kolesnikova TV, Hemler ME (2001a) EWI-2 is a major CD9 and CD81 partner and member of a novel Ig protein subfamily. J Biol Chem 276:40545–40554PubMedGoogle Scholar
  305. Stipp CS, Orlicky D, Hemler ME (2001b) FPRP, a major, highly stoichiometric, highly specific CD81- and CD9-associated protein. J Biol Chem 276:4853–4862PubMedGoogle Scholar
  306. Stipp CS, Kolesnikova TV, Hemler ME (2003) Functional domains in tetraspanin proteins. Trends Biochem Sci 28:106–112PubMedGoogle Scholar
  307. Stoeck A, Keller S, Riedle S et al (2006) A role for exosomes in the constitutive and stimulus-induced ectodomain cleavage of L1 and CD44. Biochem J 393:609–618PubMedGoogle Scholar
  308. Stoorvogel W, Kleijmeer MJ, Geuze HJ et al (2002) The biogenesis and functions of exosomes. Traffic 3:321–330PubMedGoogle Scholar
  309. Stracke ML, Liotta LA (1992) Multi-step cascade of tumor cell metastasis. In Vivo 6:309–316PubMedGoogle Scholar
  310. Subra C, Laulagnier K, Perret B et al (2007) Exosome lipidomics unravels lipid sorting at the level of multivesicular bodies. Biochimie 89:205–212PubMedGoogle Scholar
  311. Suzuki-Inoue K, Fuller GL, García A et al (2006) A novel Syk-dependent mechanism of platelet activation by the C-type lectin receptor CLEC-2. Blood 107:542–549PubMedGoogle Scholar
  312. Szala S, Kasai Y, Steplewski Z et al (1990) Molecular cloning of cDNA for the human tumor-associated antigen CO-029 and identification of related transmembrane antigens. Proc Natl Acad Sci USA 87:6833–6837PubMedGoogle Scholar
  313. Szöllósi J, Horejsí V, Bene L et al (1996) Supramolecular complexes of MHC class I, MHC class II, CD20, and tetraspan molecules (CD53, CD81, and CD82) at the surface of a B cell line JY. J Immunol 157:2939–2946PubMedGoogle Scholar
  314. Tagawa K, Arihiro K, Takeshima Y et al (1999) Down-regulation of KAI1 messenger RNA expression is not associated with loss of heterozygosity of the KAI1 gene region in lung adenocarcinoma. Jpn J Cancer Res 90:970–976PubMedGoogle Scholar
  315. Takahashi M, Sugiura T, Abe M et al (2007) Regulation of c-Met signaling by the tetraspanin KAI-1/CD82 affects cancer cell migration. Int J Cancer 121:1919–1929PubMedGoogle Scholar
  316. Takaoka A, Hinoda Y, Satoh S et al (1998) Suppression of invasive properties of colon cancer cells by a metastasis suppressor KAI1 gene. Oncogene 16:1443–1453PubMedGoogle Scholar
  317. Takeda T, Hattori N, Tokuhara T et al (2007a) Adenoviral transduction of MRP-1/CD9 and KAI1/CD82 inhibits lymph node metastasis in orthotopic lung cancer model. Cancer Res 67:1744–1749PubMedGoogle Scholar
  318. Takeda Y, Kazarov AR, Butterfield CE et al (2007b) Deletion of tetraspanin Cd151 results in decreased pathologic angiogenesis in vivo and in vitro. Blood 109:1524–1532PubMedGoogle Scholar
  319. Takenawa T, Suetsugu S (2007) The WASP-WAVE protein network: connecting the membrane to the cytoskeleton. Nat Rev Mol Cell Biol 8:37–48PubMedGoogle Scholar
  320. Takino T, Miyamori H, Kawaguchi N et al (2003) Tetraspanin CD63 promotes targeting and lysosomal proteolysis of membrane-type 1 matrix metalloproteinase. Biochem Biophys Res Commun 304:160–166PubMedGoogle Scholar
  321. Tanaka F, Hori N, Sato K (2002) Identification of differentially expressed genes in rat hepatoma cell lines using subtraction and microarray. J Biochem 131:39–44PubMedGoogle Scholar
  322. Tarasova NI, Rice WG, Michejda CJ (1999) Inhibition of G-protein-coupled receptor function by disruption of transmembrane domain interactions. J Biol Chem 274:34911–34915PubMedGoogle Scholar
  323. Telese F, Bruni P, Donizetti A et al (2005) Transcription regulation by the adaptor protein Fe65 and the nucleosome assembly factor SET. EMBO Rep 6:77–82PubMedGoogle Scholar
  324. Testa JE, Brooks PC, Lin JM et al (1999) Eukaryotic expression cloning with an antimetastatic monoclonal antibody identifies a tetraspanin (PETA-3/CD151) as an effector of human tumor cell migration and metastasis. Cancer Res 59:3812–3820PubMedGoogle Scholar
  325. Todeschini RA, Hakomori SI (2008) Functional role of glycosphingolipids and gangliosides in control of cell adhesion, motility, and growth, through glycosynaptic microdomains. Biochim Biophys Acta 1780:421–433Google Scholar
  326. Todeschini AR, Dos Santos JN, Handa K et al (2008) Ganglioside GM2/GM3 complex affixed on silica nanospheres strongly inhibits cell motility through CD82/cMet-mediated pathway. Proc Natl Acad Sci USA 105:1925–1930PubMedGoogle Scholar
  327. Tohami T, Drucker L, Shapiro H et al (2007) Overexpression of tetraspanins affects multiple myeloma cell survival and invasive potential. FASEB J 21:691–699PubMedGoogle Scholar
  328. Tokuhara T, Hasegawa H, Hattori N et al (2001) Clinical significance of CD151 gene expression in non-small cell lung cancer. Clin Cancer Res 7:4109–4114PubMedGoogle Scholar
  329. Tonoli H, Barrett JC (2005) CD82 metastasis suppressor gene: a potential target for new therapeutics? Trends Mol Med 11:563–570PubMedGoogle Scholar
  330. Tsai YC, Mendoza A, Mariano JM et al (2007) The ubiquitin ligase gp78 promotes sarcoma metastasis by targeting KAI1 for degradation. Nat Med 13:1504–1509PubMedGoogle Scholar
  331. Tsitsikov EN, Gutierrez-Ramos JC, Geha RS (1997) Impaired CD19 expression and signaling, enhanced antibody response to type II T independent antigen and reduction of B-1 cells in CD81-deficient mice. Proc Natl Acad Sci USA 94:10844–10849PubMedGoogle Scholar
  332. Tsukita S, Furuse M (2000) The structure and function of claudins, cell adhesion molecules at tight junctions. Ann N Y Acad Sci 915:129–135PubMedGoogle Scholar
  333. Tsukita S, Yonemura S (1999) Cortical actin organization: lessons from ERM (ezrin/radixin/moesin) proteins. J Biol Chem 274:34507–34510PubMedGoogle Scholar
  334. Tsutsumi S, Shimura T, Morinaga N et al (2005) Loss of KAI1 expression in gastric cancer. Hepatogastroenterology 52:281–284PubMedGoogle Scholar
  335. Ueda T, Ichikawa T, Tamaru J et al (1996) Expression of the KAI1 protein in benign prostatic hyperplasia and prostate cancer. Am J Pathol 149:1435–1440PubMedGoogle Scholar
  336. Valadi H, Ekström K, Bossios A et al (2007) Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol 9:654–659PubMedGoogle Scholar
  337. van Niel G, Porto-Carreiro I, Simoes S, Raposo G (2006) Exosomes: a common pathway for a specialized function. J Biochem 140:13–21PubMedGoogle Scholar
  338. Walker JW (2008) Protein scaffolds, lipid domains and substrate recognition in protein kinase C function: implications for rational drug design. Handb Exp Pharmacol 186:185–203PubMedGoogle Scholar
  339. Wang JC, Bégin LR, Bérubé NG et al (2007a) Down-regulation of CD9 expression during prostate carcinoma progression is associated with CD9 mRNA modifications. Clin Cancer Res 13:2354–2361PubMedGoogle Scholar
  340. Wang XQ, Yan Q, Sun P et al (2007b) Suppression of epidermal growth factor receptor signaling by protein kinase C-alpha activation requires CD82, caveolin-1, and ganglioside. Cancer Res 67:9986–9995PubMedGoogle Scholar
  341. Wells A, Grandis JR (2003) Phospholipase C-gamma1 in tumor progression. Clin Exp Metastasis 20:285–290PubMedGoogle Scholar
  342. White A, Lamb PW, Barrett JC (1998) Frequent downregulation of the KAI1(CD82) metastasis suppressor protein in human cancer cell lines. Oncogene 16:3143–3149PubMedGoogle Scholar
  343. Wieckowski E, Whiteside TL (2006) Human tumor-derived vs dendritic cell-derived exosomes have distinct biologic roles and molecular profiles. Immunol Res 36:247–254PubMedGoogle Scholar
  344. Winterwood NE, Varzavand A, Meland MN et al (2006) A critical role for tetraspanin CD151 in alpha3beta1 and alpha6beta4 integrin-dependent tumor cell functions on laminin-5. Mol Biol Cell 17:2707–2721PubMedGoogle Scholar
  345. Wright MD, Geary SM, Fitter S et al (2004a) Characterization of mice lacking the tetraspanin superfamily member CD151. Mol Cell Biol 24:5978–5988PubMedGoogle Scholar
  346. Wright MD, Moseley GW, van Spriel AB (2004b) Tetraspanin microdomains in immune cell signalling and malignant disease. Tissue Antigens 64:533–542PubMedGoogle Scholar
  347. Wu Q, Ji Y, Zhang MQ, Chen YQ et al (2003) Role of tumor metastasis suppressor gene KAI1 in digestive tract carcinomas and cancer cells. Cell Tissue Res 314:237–249PubMedGoogle Scholar
  348. Xiao Z, Blonder J, Zhou M et al (2009) Proteomic analysis of extracellular matrix and vesicles. J Proteomics 72:34–45PubMedGoogle Scholar
  349. Xu L, Hynes RO (2007) GPR56 and TG2: possible roles in suppression of tumor growth by the microenvironment. Cell Cycle 6:160–165PubMedGoogle Scholar
  350. Yalaoui S, Zougbédé S, Charrin S et al (2008) Hepatocyte permissiveness to Plasmodium infection is conveyed by a short and structurally conserved region of the CD81 large extracellular domain. PLoS Pathog 4:e1000010PubMedGoogle Scholar
  351. Yamamoto H, Vibitketkumnuen A, Adachi Y et al (2004) Association of matrilysin-2 (MMP-26) expression with tumor progression and activation of MMP-9 in esophageal squamous cell carcinoma. Carcinogenesis 25:2353–2360PubMedGoogle Scholar
  352. Yamamoto Y, Grubisic K, Oelgeschläger M (2007) Xenopus Tetraspanin-1 regulates gastrulation movements and neural differentiation in the early Xenopus embryo. Differentiation 75:235–245PubMedGoogle Scholar
  353. Yamane H, Tachibana I, Takeda Y et al (2005) Propionibacterium acnes-induced hepatic granuloma formation is impaired in mice lacking tetraspanin CD9. J Pathol 206:486–492PubMedGoogle Scholar
  354. Yanez-Mo M, Barreiro O, Gonzalo P et al (2008) MT1-MMP collagenolytic activity is regulated through association with tetraspanin CD151 in primary endothelial cells. Blood 112:3217–3226PubMedGoogle Scholar
  355. Yang J, Weinberg RA (2008) Epithelial-mesenchymal transition: at the crossroads of development and tumor metastasis. Dev Cell 14:818–829PubMedGoogle Scholar
  356. Yang X, Welch DR, Phillips KK et al (1997) KAI1, a putative marker for metastatic potential in human breast cancer. Cancer Lett 119:149–155PubMedGoogle Scholar
  357. Yang X, Claas C, Kraeft SK et al (2002) Palmitoylation of tetraspanin proteins: modulation of CD151 lateral interactions, subcellular distribution, and integrin-dependent cell morphology. Mol Biol Cell 13:767–781PubMedGoogle Scholar
  358. Yang X, Kovalenko OV, Tang W et al (2004) Palmitoylation supports assembly and function of integrin-tetraspanin complexes. J Cell Biol 167:1231–1240PubMedGoogle Scholar
  359. Yang XH, Kovalenko OV, Kolesnikova TV et al (2006) Contrasting effects of EWI proteins, integrins, and protein palmitoylation on cell surface CD9 organization. J Biol Chem 281:12976–12985PubMedGoogle Scholar
  360. Yang XH, Richardson AL, Torres-Arzayus MI et al (2008) CD151 accelerates breast cancer by regulating alpha 6 integrin function, signaling, and molecular organization. Cancer Res 68:3204–3213PubMedGoogle Scholar
  361. Yates AJ, Rampersaud A (1998) Sphingolipids as receptor modulators. An overview. Ann N Y Acad Sci 845:57–71PubMedGoogle Scholar
  362. Yauch RL, Hemler ME (2000) Specific interactions among transmembrane 4 superfamily (TM4SF) proteins and phosphoinositide 4-kinase. Biochem J 351:629–637PubMedGoogle Scholar
  363. Yauch RL, Berditchevski F, Harler MB et al (1998) Highly stoichiometric, stable, and specific association of integrin alpha3beta1 with CD151 provides a major link to phosphatidylinositol 4-kinase, and may regulate cell migration. Mol Biol Cell 9:2751–2765PubMedGoogle Scholar
  364. Yauch RL, Kazarov AR, Desai B et al (2000) Direct extracellular contact between integrin alpha(3)beta(1) and TM4SF protein CD151. J Biol Chem 275:9230–9238PubMedGoogle Scholar
  365. Yoshida T, Kawano Y, Sato K et al (2008) A CD63 mutant inhibits T-cell tropic human immunodeficiency virus type 1 entry by disrupting CXCR4 trafficking to the plasma membrane. Traffic 9:540–558PubMedGoogle Scholar
  366. You Z, Saims D, Chen S et al (2002) Wnt signaling promotes oncogenic transformation by inhibiting c-Myc-induced apoptosis. J Cell Biol 157:429–440PubMedGoogle Scholar
  367. Yunta M, Lazo PA (2003) Tetraspanin proteins as organisers of membrane microdomains and signalling complexes. Cell Signal 15:559–564PubMedGoogle Scholar
  368. Zakharova L, Svetlova M, Fomina AF (2007) T cell exosomes induce cholesterol accumulation in human monocytes via phosphatidylserine receptor. J Cell Physiol 212:174–181PubMedGoogle Scholar
  369. Zhang X, Xu W (2008) Aminopeptidase N (APN/CD13) as a target for anti-cancer agent design. Curr Med Chem 15:2850–2865PubMedGoogle Scholar
  370. Zhang XA, Bontrager AL, Hemler ME (2001) Transmembrane-4 superfamily proteins associate with activated protein kinase C (PKC) and link PKC to specific beta(1) integrins. J Biol Chem 276:25005–25013PubMedGoogle Scholar
  371. Zhang XA, Kazarov AR, Yang X et al (2002) Function of the tetraspanin CD151-alpha6beta1 integrin complex during cellular morphogenesis. Mol Biol Cell 13:1–11PubMedGoogle Scholar
  372. Zhang XA, He B, Zhou B et al (2003a) Requirement of the p130CAS-Crk coupling for metastasis suppressor KAI1/CD82-mediated inhibition of cell migration. J Biol Chem 278:27319–27328PubMedGoogle Scholar
  373. Zhang XA, Lane WS, Charrin S et al (2003b) EWI2/PGRL associates with the metastasis suppressor KAI1/CD82 and inhibits the migration of prostate cancer cells. Cancer Res 63:2665–2674PubMedGoogle Scholar
  374. Zhao X, Lapalombella R, Joshi T et al (2007) Targeting CD37-positive lymphoid malignancies with a novel engineered small modular immunopharmaceutical. Blood 110:2569–2577PubMedGoogle Scholar
  375. Zheng ZZ, Liu ZX (2007) Activation of the phosphatidylinositol 3-kinase/protein kinase Akt pathway mediates CD151-induced endothelial cell proliferation and cell migration. Int J Biochem Cell Biol 39:340–348PubMedGoogle Scholar
  376. Zhijun X, Shulan Z, Zhuo Z (2007) Expression and significance of the protein and mRNA of metastasis suppressor gene ME491/CD63 and integrin alpha5 in ovarian cancer tissues. Eur J Gynaecol Oncol 28:179–183PubMedGoogle Scholar
  377. Zhou B, Liu L, Reddivari M et al (2004) The palmitoylation of metastasis suppressor KAI1/CD82 is important for its motility- and invasiveness-inhibitory activity. Cancer Res 64:7455–7463PubMedGoogle Scholar
  378. Zhou Z, Ran YL, Hu H et al (2008) TM4SF3 promotes esophageal carcinoma metastasis via upregulating ADAM12m expression. Clin Exp Metastasis 25:537–548PubMedGoogle Scholar
  379. Zhu GZ, Miller BJ, Boucheix C et al (2002) Residues SFQ (173–175) in the large extracellular loop of CD9 are required for gamete fusion. Development 129:1995–2002PubMedGoogle Scholar
  380. Zijlstra A, Lewis J, Degryse B et al (2008) The inhibition of tumor cell intravasation and subsequent metastasis via regulation of in vivo tumor cell motility by the tetraspanin CD151. Cancer Cell 13:221–234PubMedGoogle Scholar
  381. Zöller M (2006) Gastrointestinal tumors: metastasis and tetraspanins. Z Gastroenterol 44:573–586PubMedGoogle Scholar
  382. Zöller M (2009) Tetraspanins: push and pull in suppressing and promoting metastasis. Nat Rev Cancer 9:40–55PubMedGoogle Scholar
  383. Zvieriev V, Wang JC, Chevrette M (2005) Over-expression of CD9 does not affect in vivo tumorigenic or metastatic properties of human prostate cancer cells. Biochem Biophys Res Commun 337:498–504PubMedGoogle Scholar

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© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Department of Tumor Cell BiologyUniversity Hospital of SurgeryHeidelbergGermany
  2. 2.Department of Tumor Progression and Immune DefenseGerman Cancer Research CenterHeidelbergGermany
  3. 3.Department of Applied GeneticsUniversity of KarlsruheKarlsruheGermany

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