Interactions Between CD44 and Hyaluronic Acid: Their Role in Tumor Growth and Metastasis

  • M. S. Sy
  • D. Liu
  • R. Schiavone
  • J. Ma
  • H. Mori
  • Y. Guo
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 213/3)


Adhesion molecules enable lymphocytes to interact with antigen-presenting cells or target cells more effectively (Springer 1990; Butcher 1986; Stoolman 1989). Adhesion molecules also allow lymphocytes or monocytes to interact with endothelial cells or high endothelial venules (HEV). Adhesion molecules enable lymphocytes or monocytes to recirculate and home to specific anatomical sites during inflammation. Tumor metastasis is a complex phenomenon involving a sequence of events that remain poorly understood (Fidler 1978; Nicolson 1988; Kahn 1992; Stetler-Stevenson et al. 1993; Turley 1984). Tumor metastatic cascade involves tumor cell and host cell interactions and may also involve interactions among tumor cells. Tumor cells developed in different microenvironments may utilize different mechanisms for invasion and metastasis. This interpretation was supported by results obtained from experiments using orthoptopic implantation of human carcinoma cells in nude mice (Fidler and Radinsky 1990; Fidler et al. 1990). Human colon carcinoma cell lines do not metastasize unless they are injected into the cecum or spleen of nude mice (Fidler 1991). Subcutaneous injection of the same tumor cell lines results in a significantly lower frequency of metastasis formation. These observations have also been observed with human breast, stomach, pancreas, and prostate tumor cell lines (Fidler and Radinsky 1990; Fidler 1990, 1991). In general, orthotopic transplants of human tumors into nude mice favors recapitulation of the metastatic patterns seen in patients with the same tumor.


Hyaluronic Acid Tumor Cell Line Sialic Acid Cytoplasmic Domain Human Tumor Cell Line 
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.


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  1. Alho AM, Underhill CB (1989) The hyaluronate receptor is preferentially expressed on proliferating epithelial cells. J Cell Biol 108: 1557–1565PubMedGoogle Scholar
  2. Altomonte M, Colizzi F, Esposito G, Maio M (1993) Circulating intercellular adhesion molecule 1 as a marker of disease progression in cutaneous melanoma. N Engl J Med 327: 959Google Scholar
  3. Andres JL, Stanley K, Cheifetz K, Massague J (1989) Membrane anchored and soluble forms of betaglycan, a polymorphic proteoglycan that binds transforming growth factor B. J Cell Biol 109: 3137–3145PubMedGoogle Scholar
  4. Aruffo A, Stamenkovic I, Melnick M, Underhill CB, Seed B (1990) CD44 is the principal cell surface receptor for hyaluraonate. Cell 61: 1303–1311PubMedGoogle Scholar
  5. Asplund T, Heldin P (1994) Hyaluronan receptors are expressed on human malignant mesothelioma cells but not on normal mesothelial cells. Cancer 54: 4516–4523Google Scholar
  6. Bartolazzi A, Peach R, Aruffo A, Stamenkovic I (1994) Interaction between CD44 and hyaluronate is directly implicated in the regulation of tumor development. J Exp Med 180: 53–66PubMedGoogle Scholar
  7. Bazil V, Horejsi V (1992) Shedding of the CD44 adhesion molecules from leukocytes induced by anti-CD44 monoclonal antibody stimulating the effect of a natural receptor ligand. J Immunol 149: 747–753PubMedGoogle Scholar
  8. Bennet KL, Jackson DG, Simon JC et al (1995) CD44 isoforms containing exon V3 are responsible for the presentation of heparin binding growth factor. J Cell Biol 128: 687–698Google Scholar
  9. Birch M, Mitchell S, Hart IR (1991) Isolation and characterization of human melanoma variants expressing high and low levels of CD44. Cancer Res 51: 6660–6667PubMedGoogle Scholar
  10. Bourguignon LYW, Kalomiris EL, Lokeshwar VB (1991) Acylation of the lymphoma transmembrane glycoprotein GP85, may be required for GP-85 ankyrin interaction. J Biol Chem 266: 1761–1765Google Scholar
  11. Brown TA, Bouchard T, St. John T, Wayner E, Carter WG (1991) Human keratinocytes express a new CD44 core protein (CD44E) as a heparin sulfate intransic membrane proteoglycan with additional exons. J Cell Biol 113: 207–216PubMedGoogle Scholar
  12. Budd RC, Cerottini C, Horvath C et al. (1987) Distinction of virgin and memory T lymphocytes: stable acquisition of the Pgp-1 glycoprotein concomitant with antigenic stimulation. J Immunol 138: 3120–3129PubMedGoogle Scholar
  13. Butcher EC (1986) The regulation of lymphocytes traffic. Curr Top Microbiol Immunol 128: 85–124PubMedGoogle Scholar
  14. Camp RL, Kraus TS, Birkeland L, Pure E (1991) High levels of CD44 expression distinguish virgin from antigen primed B cells. J Exp Med 173: 763–766PubMedGoogle Scholar
  15. Camp RL, Kraus TA, Pure E (1992) Variations in the cytoskeletal interaction and post translational modifications of the CD44 homing receptor in macrophages. J Cell Biol 115: 1283–1292Google Scholar
  16. Cannistra SP, Kanasa GS, Niloff J, DeFranzo B, Kim Y, Ottensmeier C (1993) Binding of ovarian cancer cells to peritoneal mesothelium in vitro is partly mediated by CD44 H. Cancer Res 53: 3830–3838PubMedGoogle Scholar
  17. Carter WG, Wayner EA (1988) Characterization of the class III collagen receptor, a phosphorylated, transmembrane glycoprotein expressed in nucleared human cells. J Biol Chem 263: 4193–4201PubMedGoogle Scholar
  18. Chandrasekhar S, Kleinman HK, Rasseil JR (1983) Interaction of link protein with collagen. J Biol Chem 258: 6226–6231PubMedGoogle Scholar
  19. Classen SD, Eierman W, Wolf H, Kopp R, Wilmans W (1995) CD44 variant in serum of breast cancer?patients: a prognostic factor for clinical progresison? Proc Am Assoc Cancer Res 36:209Google Scholar
  20. Cross AS, Wright DG (1991) Mobilization of sialidase from intracellular stores to the surface of human neutrophils and its role in stimulated adhesion responses of these cells. J Clin Invest 88: 2067–2076PubMedGoogle Scholar
  21. Culty M, Miyake K, Underhill CB (1992) Binding and degradation of hyaluronan by human breast cancer cell lines expresssion different forms of CD44; correlation with invasive potential. J Cell Physiol 160: 275–286Google Scholar
  22. Deak F, Kiss I, Sparks KJ, Argraves WS, Hampikian G, Foetinck PF (1986) Complete amino acid sequence of chicken cartilage link protein deduced from cDNA clones. Proc Natl Acad Sci USA 83: 3766–3770PubMedGoogle Scholar
  23. DeGasperi R, Thomas LJ, Sugiyama E et al (1990) Correction of a defect in mammalian GPI anchor biosynthesis by a transfected yeast gene. Science 250: 988–991PubMedGoogle Scholar
  24. Denning SM, Lee PT, Singer KH, Haynes BF (1990) Antibodies against the CD44 p80, lymphocyte homing receptor molecule augment human peripheral blood T cell activation. J Immunol 144: 7–15PubMedGoogle Scholar
  25. Dennis J, Waller C, Timpl R, Schirmacher V (1982) Surface sialic acid reduces attachment of metastatic tumor cells to collagen type IV and fibronectin. Nature 300: 274–276PubMedGoogle Scholar
  26. Doege K, Sasaki M, Horigan E, Hassel J, Yamada Y (1987) Complete primary structure of the rat cartilage proteoglycan core protein deduced from cDNA sequences. J Biol Chem 262: 17757–17763PubMedGoogle Scholar
  27. Faassem AE, Schräger JA, Klein DJ, Oegema TR, Couchman JR, McCarthy JB (1992) A cell surface chondroitin sulfate proteoglycan, immunologically related to CD44 is involved in type collagen mediated melanoma cell motility and invasion. J Cell Biol 116: 521–531Google Scholar
  28. Fidler IJ (1978) Tumor heterogeneity and the biology of cancer invasion and metastasis. Cancer Res 38: 2651–2660PubMedGoogle Scholar
  29. Fidler IJ (1991) Orthotopic implantation of human colon carcinomas into nude mice provides a valuable model for the biology and therapy of metastasis. Cancer Metastasis Rev 10: 229–243PubMedGoogle Scholar
  30. Fidler IJ, Radinsky R (1990) Genetic control of cancer metastasis. J Natl Cancer Inst 82: 166–168PubMedGoogle Scholar
  31. Fidler IJ, Naito S, Pathak S (1990) Orthotopic implantation is essential for the selection, growth and metastasis of human renal cell cancer in nude mice. Cancer Metastasis Rev 9: 149–165PubMedGoogle Scholar
  32. Fogel M, Altevogt P, Schiramacher V (1983) metastatic potential severely altered by changes in tumor cell adhesiveness and cell surface sialylation. J Exp Med 157: 371–376PubMedGoogle Scholar
  33. Folkman J, Klagsbum M (1987) Angiogenesis factors. Science 235: 442–447PubMedGoogle Scholar
  34. Folkman J (1991) Tumor angiogenesis. In: Holland JF (ed) Cancer medicine. Lee and Febiger, PhiladelphiaGoogle Scholar
  35. Fox SB, Gatter KC, Jackson DG et al (1993) CD44 and cancer screening. Lancet 342: 548–549PubMedGoogle Scholar
  36. Fox SB, Fawcett J, Jackson DG et al (1994) Normal human tissues, in addition to some tumors, express multiple different CD44 isoforms. Cancer Res 54: 4539–4546PubMedGoogle Scholar
  37. Fujita N, Yaegashi K, Ide Y et al (1994) Expression of CD44 in normal versus tumor endometrial tissues: possible implication of reduced expression of CD44 in lymph-vascular space involvement of cancer cells. Cancer Res 54: 3922–3928PubMedGoogle Scholar
  38. Gross N, Beretta C, Eruisseau GM, Jackson D, Simmons D, Beck D (1994) CD44H expression by human neuroblastoma cells: relation to MYCN amplication and lineage differentiation. Cancer Res 54: 4238–4242PubMedGoogle Scholar
  39. Gunthert U, Hofman M, Rudy S et al (1991) A new variant of glycoprotein CD44 congers metastatic potential to rat carcinoma cells. Cell 65: 13–24PubMedGoogle Scholar
  40. Guo YJ, Ma J, Wong H et al. (1993) Monoclonal anti-CD44 antibody acts in synergy with anti-CD2 but inhibtis anti-CD3 or T cell receptor mediated signaling in murine T cell hybridomas. Cell Immunol 153: 186–191Google Scholar
  41. Guo YJ, Ling SC, Wong, Sy MS (1994) Acylation of CD44 may interfere with CD3 mediated signaling in human lymphocytes. Int Immunol 6(2): 213–221PubMedGoogle Scholar
  42. Guo YJ, Ma J, Wang JH et al (1994) Inhibition of human melanoma growth and metastasis in vivo by anti-CD44 monoclonal antibody. Cancer Res 54: 1561–1565PubMedGoogle Scholar
  43. Guo YJ, Liu GG, Wang XN et al (1994) Soluble CD44 in the serum as an indicator of tumor growth and metastasis in patients with gastric or colon cancer. Cancer Res 54: 422–426PubMedGoogle Scholar
  44. Hanning R, Mainolfi E, Bystryn JC, Henn M, Merluzzi VJ, Rothlein R (1991) Serum levels of circulating intercellular adhesion molecule 1 expression in human malignant melanoma. Cancer Res 51: 5003–5005Google Scholar
  45. Hardingham TE, Hosang AJ (1992) proteoglycans: many forms and many functions. FASEB J 6: 861–870PubMedGoogle Scholar
  46. Hardwick C, Hoare K, Owens R et al (1992) Molecular cloning of a novel hyaluronan receptor that mediates tumor cell motility. J Cell Biol 117: 1343–1350PubMedGoogle Scholar
  47. Hart I, Birch M, Marshall JF (1991) Cell adhesion receptor expression during melanoma progression and metastasis. Cancer Metastasis Rev 10: 115–135PubMedGoogle Scholar
  48. Haynes BF, Telen MJ, Hale LP, Denning SM (1989) CD44 a molecule involved in leukocyte adherence and T cell activation. Immunol Today 10: 423–427PubMedGoogle Scholar
  49. Haynes BF, Hale LP, Patton KL, Martin ME, McCallum RM (1991) Measurement of an adhesion molecule as an indicator of inflammatory disease activity. UP-regulation of the receptor for hyaluronate (CD44) in rheumatoid arthritis. Arthritis Rheum 34: 1434–1441PubMedGoogle Scholar
  50. Heider K-H, Hofmann M, Hors E et al. (1993) A human homologue of the rat metastasis associated variant of CD44 is expressed in colorectal carcinomas and adenomatous polyps. J Cell Biol 120: 227–233PubMedGoogle Scholar
  51. Herlyn M, Rodeck U, Koprowski H (1987) Shedding of human tumor associated antigens in vitro and in vivo. Adv Cancer Res 49: 189–221PubMedGoogle Scholar
  52. Herrlich P, Rudy W, Hofmann M et al. (1993) CD44 and splice variants of CD44 in normal differentiation and tumor progression. In: Hemler M, Mihich E (eds) Cell adhesion molecules. Plenum, New York, pp 265–288Google Scholar
  53. Hoessli DC (1980) T lymphocyte differentiation is accompanied by increase in sialic acid content of Thy-1 antigen. Nature 283: 576–577PubMedGoogle Scholar
  54. Hofmann U, Rudy W, Zooler M et al (1991) CD44 splice variants confer metastatic behavior in rats: homologous sequences are expressed in human tumor cell lines. Cancer Res 51: 5292–5297PubMedGoogle Scholar
  55. Horai T, Nakamura N, Tateishi R, Hattori S (1981) Glycosaminoglycans in human lung cancer. Cancer 48: 2016–2021.PubMedGoogle Scholar
  56. Horst E, Meijer CJ, Radaszkiewicz T, Oseloppele GJ, Van Krieken JH, Pals ST (1990) Adhesion molecules in the prognosis of diffuse lage-cell lymphoma: expression of a lymphocyte homing receptor (CD44), LFA-1, (CD11a/18) and ICAM-1 (CD54). Leukemia 4: 595–599PubMedGoogle Scholar
  57. Huet SH, Groux H, Caillou B, Valentin H, Prieur AM, Bernard A (1989) CD44 contributes to T cell activation. J Immunol 143: 798–801PubMedGoogle Scholar
  58. Hughes EN, Mengod G, August JT (1981) Murine cell surface glycoproteins. Characterization of a major components of 80,000 daltons as a polymorphic differentiation antigen of mesenchyma cells. J Biol Chem 256: 7023–7027PubMedGoogle Scholar
  59. Jalkanen S, Bargatze RF, del los Toyos J, Butcher EC (1987) Lymphocyte recognition of high endothelium: antibodies to distinct epitopes of an 85–95-kD glycoprotein antigen differentially inhibit lymphocyte binding to lymph node, mucosal, or synovial endothelial cells. J Cell Biol 105: 983–990PubMedGoogle Scholar
  60. Jalkanen S, Jalknen M (1992) Lymphocyte CD44 binds the COOH-terminal heparin binding domain of fibronectin. J Cell Biol 116: 817–825PubMedGoogle Scholar
  61. Kageshita T, Yoshii A, Kimura T et al (1993) Clinical relevance of ICAM-1 expression in primary lesions and serum of patients with malignant melanoma. Cancer Res 53: 4927–4932PubMedGoogle Scholar
  62. Kahn P (1992) Adhesion protein studies provide new clue to metastasis. Science 257: 614–615PubMedGoogle Scholar
  63. Kalomiris EL, Bourguignon LYW (1988a) Mouse T lymphoma cells contain a transmembrane glycoprotein (GP85) that binds ankyrin. J Cell Biol 106: 319–327PubMedGoogle Scholar
  64. Kalomiris EL, Bourguignon LYW (1988b) Lymphoma protein kinase C is associated with the transmembrane glycoprotein gp85, and may function in gp85 ankyrin binding. J Biol Chem 264: 8113–8120Google Scholar
  65. Katoh S, McCarthy JB, Kincade PW (1994) Characterization of soluble CD44 in the circulation of mice: levels are affected by immune activity and tumor growth. J Immunol 152: 3441–3449Google Scholar
  66. Kennel SJ, Lankford TK, Foote LJ, Shinpock SG, Stringer C (1993) CD44 expression of murine tissues. J Cell Sci 104: 373–382PubMedGoogle Scholar
  67. Kiefer MC, Stephans JC, Crawford K, Okino K, Barr PJ (1990) Ligand affinity cloning and structure of a cell surface heparan sulfate proteoglycan that binds basic fibroblast growth factor. Proc Natl Acad Sci USA 87: 6985–6989PubMedGoogle Scholar
  68. Knudson W, Biswas C, Li X-Q, Nemec RE, Toole BP (1989) The role and regulation of tumor associated hyaluronan. The biology of hyaluronan. Ciba Found Symp 143: 150–160Google Scholar
  69. Knutson JR, Fields GB, Lida J, Miles AJ, McCarthy JB (1995) A type IV collagen derived synthetic peptide, IN-H1, interacts with human melanoma CD44 chondroitin sulfate proteoglycan and inhibitis invasion of basement membranes. Proc Am Assoc Cancer Res 36: 68Google Scholar
  70. Koopman G, Heider K-H, Horst E et al. (1993) Activated human lymphocytes and aggressive non-Hodgkin’s lymphomas express a homologue of the rat metastasis associated variant of CD44. J Exp Med 177: 897–904PubMedGoogle Scholar
  71. Krusius T, Gehlsen KR, Ruoslahti E (1987) A fibroblast chondroitin sulfate proteoglycan core protein contains lectin like and growth factor like sequence. J Cell Biol 262: 13120–13125Google Scholar
  72. Lacy BE, Underhill CB (1987) The hyaluronate receptor is associated with actin filaments. J Cell Biol 105: 1395–1404PubMedGoogle Scholar
  73. Laurent TC, Fraser JRE (1992) Hyaluronan. FASEB J 6: 2397–2404PubMedGoogle Scholar
  74. Lee TH, Wisniewski H-G, Vilcek J (1992) A novel secretory tumor necrosis factor inducible protein is a member of the family of hyaluronate binding proteins closely related to the adhesion receptor CD44. J Cell Biol 116: 545–557PubMedGoogle Scholar
  75. Legras S, Gunthert U, Li Y et al. (1995) CD44 alternative splicing in normal human myelopoiesis and its deregulation in acute myeloblastic leukemia (AML). Proc Am Assoc Cancer Res 36: 465–465Google Scholar
  76. Lesley J, Schulte R, Hyman R (1990) Binding of hyaluronic acid to lymphoid cell lines is inhibited by monoclonal antibodies against Pgp-1. J Exp Cell Res 187: 224–229Google Scholar
  77. Lesley J Q H, Miyake K, Hamann A, Hyman R, Kincade PW (1992) Requirements for hyaluronic acid binding by CD44: a role for the cytoplasmic domain and activation by antibody. J Exp Med 172: 257–266Google Scholar
  78. Lesley J, Hyman R, Kincade PL (1993) CD44 and its interaction with extracellular matrix. Adv Immunol 34: 271–335Google Scholar
  79. Liao HX, Levesqjue MC, Patton K et al (1993) Regulation of human CD44H and CD44E isoform binding to hyaluronan by phorbol myristate acetate and anti-CD44 monoclonal and polyclonal antibodies. J Immnol 151: 6490–6499Google Scholar
  80. Lloyd CW (1975) Sialic acid and the social behavior of cells. Biol Rev 50: 325–350PubMedGoogle Scholar
  81. Lokeshwar VB, Bourguignon LYW (1992) The lymphoma transmembrane glycoprotein GP85 (CD44) is a novel guanine nucleotide binding protein which regulates GP85 (CD44)-ankyrin interaction. J Biol Chem 267: 22073–22078PubMedGoogle Scholar
  82. Lucas MG, Green AM, Telen MJ (1989) Characterization of the serum In (Lu)-related antigen: identification of a serum protein related to erythrocyte p80. Blood 73: 596–600PubMedGoogle Scholar
  83. Lynch F, Ceredig R (1988) Lyt24 (Pgp-1) expression by thymocytes and peripheral T cells. Immunol Today 9: 7–10PubMedGoogle Scholar
  84. MacLeod CL, Weinroth SE, Sterifinger C, Glaser SM, Hays EF (1985) SL12 murine T lymphoma: a new model for tumor cell heterogeneity. J Natl Cancer Inst 74: 875–879PubMedGoogle Scholar
  85. Matsumura Y, Tarin D (1993) Significance of CD44 gene products for cancer diagnosis and disease evaluation. Lancet 340: 1053–1058Google Scholar
  86. Matsumura Y, Smith S, Tarin JC (1995) Cancer diagnosis by detection of new abnormalities in splicing of CD44 gene products in bladder tumors and urine cell sediments. Proc Am Assoc Cancer Res 36: 283Google Scholar
  87. Merzak A, Koocheckpour S, Pilkington GJ (1994) CD44 mediates human glioma cell adhesion and invasion in vitro. Cancer Res 54: 3988–3992PubMedGoogle Scholar
  88. Miyake K, Underhill CB, Lesley J, Kincade PW (1989) Hyaluronate can function as a cell adhesion molecule and£D44 participates in hyaluronate recognition. J Exp Med 172: 69–75Google Scholar
  89. Murakami S, Miyake K, June CH, Kincade PW, Hodes RJ (1990) IL-5 induces a Pgp-1 bright B cell subpopulation that is highly enriched in proliferative and Ig secretory activity and binds hyaluronate. J Immunol 145: 3618–3627PubMedGoogle Scholar
  90. Murakami S, Miyake K, Bel R, Kincade PW, Hodes RJ (1991) Characterization of autoantibody secreting B cells in mice stimulatory chronic graft versus host reactions: identification of a CD44 high population that binds specifically to hyaluronate. J Immunol 146: 1422–1427PubMedGoogle Scholar
  91. Murakami S, Shimabukuro Y, Miki Y et al (1994) Inducible binding of human lymphocytes to hyaluronate via CD44 does not require cytoskeleton association but does require new protein synthesis. J Immunol 152: 467–477PubMedGoogle Scholar
  92. Nagabhushan M, PretlowTG, Guo YJ, Amini SB, PretlowTP, Sy MS (1995) Altered expression of CD44 in prostate cancer metastases (submitted)Google Scholar
  93. Nemec RE, Toole BP, Knudson (1987) The cell surface hyaluronate binding sites of invasive human bladder carcinoma cells. Biochem Biophy Res Commun 149: 249–257Google Scholar
  94. Nicolson GL (1988) Organ specificity of tumor metastasis: role of preferential adhesion, invasion and growth of malignant cells at specific secondary sites. Cancer Metastasis Rev 7: 143–188PubMedGoogle Scholar
  95. Nottenburg C, Rees G, St. John T (1989) Isolation of mouse CD44 cDNA: structure features are distinct from the primate cDNA. Proc Natl Acad Sci USA 86: 8521–8525PubMedGoogle Scholar
  96. Oyama F, Hiroshashi S, Shimosato Y, Titani K, Sekiguchi K (1989) Deregulation of alternative splicing of fibronectin pre-mRNA in malignant human liver tumors. J Biol Chem 264: 10331–10334PubMedGoogle Scholar
  97. Payne LN, Pani PK, Weiss RA (1971) A domain epistatic gene which inhibits cellular susceptibility to RSV. J Gen Virol 13: 455–462PubMedGoogle Scholar
  98. Peach RJ, Hollenbaugh D, Stamemkovic I, Aruffo A (1993) Identification of hyaluronic acid binding sites in the extracellular domain of CD44. J Cell Biol 122: 257–264PubMedGoogle Scholar
  99. Peacock EEJ (1984) Wound repair, 3rd edn. Saunders, PhiladelphiaGoogle Scholar
  100. Penno MB, August JT, Baylin SB et al (1994) Expression of CD44 in human lung tumors. Cancer Res 54: 1381–1387PubMedGoogle Scholar
  101. Perschl A, Lesley J, English N, Trowbridge I, Hyman R (1995) Role of CD44 cytoplasic domain in hyaluronan binding. Eur J Immunol 25: 495–501PubMedGoogle Scholar
  102. Philipson LH, Schwartz NB (1984) Subcellular localization of hyaluronate synthetase in oligoden-drocytoma cells. J Biol Chem 259: 5017–5023PubMedGoogle Scholar
  103. Picker LJ, Nakache M, Butcher EC (1989) Monoclonal antibodies to human lymphocytes homing receptors define a novel class of adhesion molecules on diverse cell types. J Cell Biol 109: 927–935PubMedGoogle Scholar
  104. Poole AR (1986) Proteoglycans in health and disease: structure and functions. Biochem J 236: 1–14PubMedGoogle Scholar
  105. Reid T, Flint MH (1974) Changes in glycosaminoglycan content of healing rabbit tendon. J Embryol Exp Morphol 31: 489–495PubMedGoogle Scholar
  106. Rothbard JB, Brackenbury R, Cunnigham AB, Edelman GM (1982) Differences in the carbohydrate structures of neural adhesion molecules from adult and embryonic chicken brains. J Biol Chem 257: 11064–11069PubMedGoogle Scholar
  107. Rothman BL, Blue M, Kelley KA, Wunderlich D, Mierz DV, Aune TM (1991) Human T cell activation of OKT3 is inhibited by a monoclonal antibody to CD44. J Immunol 147: 2493–2497PubMedGoogle Scholar
  108. Rouslahti E (1988) Structure and biology of proteoglycans. Ann Rev Cell Biol 4: 229–255Google Scholar
  109. Ruoslahti E, Yamagushi Y (1991) Proteoglycans as modulators of growth factor activities. Cell 64: 867–869PubMedGoogle Scholar
  110. Saksela Of Rifkin DB (1990) Release of basic fibroblast growth factor-heparan sulfate complexes from endothelial cells by plasminogen activated mediated proteolytic activity. J Cell Biol 110: 767–775PubMedGoogle Scholar
  111. Salmi M, Gron-Virta K, Sointu P, Grenman R, Kalimo H, Jalkannen S (1993) Regulated expression of exon V6 containing isoforms of CD44 in man: downregulation during malignant transformation of tumors of squamocellular origin. J Cell Biol 122: 431–442PubMedGoogle Scholar
  112. Schauer R (1985) Sialic acids and their role as biological masks. Trends Biochem Sci 10: 357–360Google Scholar
  113. Schwarzbauer JE, Patel RS, Fonda D, Hynes RO (1987) Multiple sites of alternative splicing of the rat fibronectin gene transcripts. EM BO J 6: 2573–2580PubMedGoogle Scholar
  114. Screaton GR, Bell MV, Jackson DG, Cornelis FB, Gerth U, Bell JE (1992) Genomic structure of DNA encoding the lymphocyte homing receptor CD44 reveals at least 12 alternatively spliced exons. Proc Natl Acad Sci USA 89: 12160–12164PubMedGoogle Scholar
  115. Screaton GR, Bell MV, Bell Jl, Jackson D (1993) The identification of a new alternative exon with highly restricted tissue expression in transcripts encoding the mouse Pgp-1 (CD44) homing receptor. J Biol Chem 268: 12235–12238PubMedGoogle Scholar
  116. Shimizu Y, Seventer GA, Siraganian R, Wahl L, Shaw S (1989) Dual role of the CD44 molecule in T cell adhesion and activation. J Immunol 143: 2457–2463PubMedGoogle Scholar
  117. Shtivelman E, Bishop MJ (1991) Expression of CD44 is repressed in neuroblastoma cells. Mol Cell Biol 11; 5446–5453PubMedGoogle Scholar
  118. Sieweke MH, Thompson NL, Sporn MB, Bissell MJ (1990) Mediation of wound related Rous sarcoma virus tumorigenesis by TGFB. Science 248: 1656–1660PubMedGoogle Scholar
  119. Springer TA (1990) Adhesion receptors of the immune system. Nature 346: 426–434Google Scholar
  120. Stamenkovic I, Aminot M, Pesando JM, Seed B (1989) A lymphocyte molecule implicated in lymph node homing is a member of the cartilage link protein family. Cell 56: 1057–1062PubMedGoogle Scholar
  121. Stamenkovic I, Aruffo A, Aminot M, Seed B (1991) The hematopoietic and epithelial forms of CD44 are distinct polypeptides with different adhesion potentials for hyaluronate bearing cells. EMBO 10: 343–348Google Scholar
  122. Stetler-Stevenson WG, Aznavoorian S, Liotta LA (1993) Tumor cell interactions with the extracellular matrix during invasion and metastasis. Annu Rev Cell Biol 9: 541–573PubMedGoogle Scholar
  123. Stoolman LM (1989) Adhesion molecules controlling lymphocytes migration. Cell 56: 907–910PubMedGoogle Scholar
  124. Sy MS, Guo YJ, Stamenkovic I (1991) Distinct effects of two CD44 isoforms on tumor growth in vivo. J Exp Med 174: 859–866PubMedGoogle Scholar
  125. Sy MS, Guo YJ, Stamenkovic I (1992) Inhibition of tumor growth in vivo with a chimeric CD44-immunoglobulin molecule. J Exp Med 176: 623–627PubMedGoogle Scholar
  126. Takeuchi J, Sobue M, Sato E, Yoshida M, Uchibori N, Miura K (1981) A high level of glycosaminoglycan synthesis of squamous cell carcinoma of the parotid eland. Cancer 47: 2030–2035PubMedGoogle Scholar
  127. Tan PHS, Santos EB, Rossbach HC, Sandmaier BM (1993) Enhancement of natural killer activity by an antibody to CD44. J Immunol 150: 812–820PubMedGoogle Scholar
  128. Tanabe KK, Ellis LM, Saya H (1993) Expression of CD44R1 adhesion molecule in colon carcinomas and metastasis. Lancet 341: 725–726PubMedGoogle Scholar
  129. Tanaka Y, Adams DH, Hubscher S, Hirano H, Siebenlist U, Shaw S (1993) T-cell adhesion induced by proteoglycan-immobilized cytokine MIP-1B. Nature 361: 79–82PubMedGoogle Scholar
  130. Thomas LJ, DeGasperi R, Sugiyama E et al (1991) Functional analysis of T cell mutants defective in the biosynthesis of glycosyl phosphatidylinositol anchor. J Biol Chem 266: 23175–23184PubMedGoogle Scholar
  131. Thomas L, Byers HR, Vink J, Stamenkovic I (1992) CD44H regulates tumor cell migration of hyaluronate coated substrate. J Cell Biol: 971–991Google Scholar
  132. Tolg C, Hofmann M, Herrlich P, Ponta H (1993) Splicing choice from ten variant exons establishes CD44 variability. Nucleic Acids Res 21: 1225–1229PubMedGoogle Scholar
  133. Toole BP (1990) Hyaluronan and its binding proteins, the hyaladherins. Curr Opin Cell Biol 2: 839–844PubMedGoogle Scholar
  134. Toole BP, Biswas C, Gross J (1979) Hyaluronate and invasiveness of the rabbit V2 carcinoma. Proc Natl Acad Sci USA 76: 6299–6303PubMedGoogle Scholar
  135. Trowbridge IS, Lesley J, Schulte R, Trotter J (1982) Biochemical characterization and cellular dis-tribution of a polymorphic, murine cell surface glycoprotein expressed on lymphoid tissues. Immunogenetics 15: 299–312PubMedGoogle Scholar
  136. Tsujisaki M, Imai K, Hirata H et al (1991) Detection of circulating intercellular adhesion molecule 1 antigen in malignant diseases. Clin Exp Immunol 85: 3–8PubMedGoogle Scholar
  137. Turley EA (1984) Proteoglycans and cell adhesion: their putative role during tumorigenesis. Cancer Metastasis Rev 3: 325–339PubMedGoogle Scholar
  138. Underhill CH, Dorfman A (1978) The role of hyaluronic acid in intercellular adhesion of cultured mouse cells. Exp Cell Res 117: 155–164PubMedGoogle Scholar
  139. Underhill CB, Toole BP (1982) Transformation-dependent loss of the hyaluronate containing coats of cultured cells. J Cell Physiol 110: 123–128PubMedGoogle Scholar
  140. Underhill CB (1982) Interaction of hyaluronate with the surface of simian virus 40-transformed 3T3 cells: aggregation and binding studies. J Cell Sci 56L: 177–189Google Scholar
  141. Webb DSS, Shimizu Y, Van Seventer GA, Shaw S, Gerrard TL (1990) LFA-3, CD44 and CD45: Physiologic triggers of human monocyte TNF and IL-1 release. Science 249: 1295–1297PubMedGoogle Scholar
  142. West DC, Sattar A, Kumar S (1985) Angiogenesis induced by the degradation products of hyaluronic acid. Science 228: 1324–1326PubMedGoogle Scholar
  143. Wielenga VJM, Heider K-H, Offerhaus GJA et al. (1993) Expression of CD44 variant proteins in humal colorectal cancer is related to tumor progression. Cancer Res 53: 4754–4756PubMedGoogle Scholar
  144. Wolffe EJ, Cause WC, Pelfrey CM, Holland SM, Steinberg AD, August JT (1990) The cDNA sequence of mouse Pgp-1 and to human CD44 cell surface antigen and proteoglycan core/link proteins. J Biol Chem 265: 341–352PubMedGoogle Scholar
  145. Woodland H, Jones L (1988) Growth factors in amphibian cell differentiation. Nature 332: 113–115PubMedGoogle Scholar
  146. Zhou DF, Ding JF, Picker LJ, Bargatze RF, Butcher EC, Goeddel DV (1989) Molecular cloning and expression of Pgp-1. The mouse homolog of the human H-CAM (Hermes) lymphocyte homing receptor. J Immunol 143: 3390–3395PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1996

Authors and Affiliations

  • M. S. Sy
    • 1
    • 2
    • 3
  • D. Liu
    • 1
  • R. Schiavone
    • 1
  • J. Ma
    • 1
  • H. Mori
    • 1
  • Y. Guo
    • 1
    • 3
  1. 1.Institute of Pathology, School of MedicineCase Western Reserve UniversityClevelandUSA
  2. 2.Department of Dermatology, School of MedicineCase Western Reserve UniversityClevelandUSA
  3. 3.Cancer Research Center, School of MedicineCase Western Reserve UniversityClevelandUSA

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