Cancer Microenvironment

, Volume 4, Issue 2, pp 199–208 | Cite as

The Role of Annexin A2 in Tumorigenesis and Cancer Progression

  • Noor A. Lokman
  • Miranda P. Ween
  • Martin K. Oehler
  • Carmela Ricciardelli
Review Paper


Annexin A2 is a calcium-dependent, phospholipid-binding protein found on various cell types. It is up-regulated in various tumor types and plays multiple roles in regulating cellular functions, including angiogenesis, proliferation, apoptosis, cell migration, invasion and adhesion. Annexin A2 binds with plasminogen and tissue plasminogen activator on the cell surface, which leads to the conversion of plasminogen to plasmin. Plasmin is a serine protease which plays a key role in the activation of metalloproteinases and degradation of extracellular matrix components essential for metastatic progression. We have recently found that both annexin A2 and plasmin are increased in conditioned media of co cultured ovarian cancer and peritoneal cells. Our studies suggest that annexin A2 is part of a tumor-host signal pathway between ovarian cancer and peritoneal cells which promotes ovarian cancer metastasis. Accumulating evidence suggest that interactions between annexin A2 and its binding proteins play an important role in the tumor microenvironment and act together to enhance cancer metastasis. This article reviews the current knowledge on the biological role of annexin A2 and its binding proteins in solid malignancies including ovarian cancer.


Annexin A2 p11 protein t-PA Plasmin and metastasis 



This research was supported by the Ovarian Cancer Research Foundation (OCRF).


  1. 1.
    Ranson M, Andronicos NM (2003) Plasminogen binding and cancer: promises and pitfalls. Front Biosci 8:s294–304PubMedCrossRefGoogle Scholar
  2. 2.
    Hajjar KA, Krishnan S (1999) Annexin II: A mediator of the plasmin/plasminogen activator system. Trends Cardiovasc Med 9:128–138PubMedCrossRefGoogle Scholar
  3. 3.
    Cesarman GM, Guevara CA, Hajjar KA (1994) An endothelial cell receptor for plasminogen/tissue plasminogen activator (t-PA). II. Annexin II-mediated enhancement of t-PA-dependent plasminogen activation. J Biol Chem 269:21198–21203PubMedGoogle Scholar
  4. 4.
    Hajjar KA, Guevara CA, Lev E et al (1996) Interaction of the fibrinolytic receptor, annexin II, with the endothelial cell surface. Essential role of endonexin repeat 2. J Biol Chem 271:21652–21659PubMedCrossRefGoogle Scholar
  5. 5.
    Mai J, Waisman DM, Sloane BF (2000) Cell surface complex of cathepsin B/annexin II tetramer in malignant progression. Biochim Biophys Acta 1477:215–230PubMedCrossRefGoogle Scholar
  6. 6.
    Vishwanatha JK, Chiang Y, Kumble KD et al (1993) Enhanced expression of annexin II in human pancreatic carcinoma cells and primary pancreatic cancers. Carcinogenesis 14:2575–2579PubMedCrossRefGoogle Scholar
  7. 7.
    Sharma MR, Koltowski L, Ownbey RT et al (2006) Angiogenesis-associated protein annexin II in breast cancer: selective expression in invasive breast cancer and contribution to tumor invasion and progression. Exp Mol Pathol 81:146–156PubMedCrossRefGoogle Scholar
  8. 8.
    Mohammad HS, Kurokohchi K, Yoneyama H et al (2008) Annexin A2 expression and phosphorylation are up-regulated in hepatocellular carcinoma. Int J Oncol 33:1157–1163PubMedGoogle Scholar
  9. 9.
    Inokuchi J, Narula N, Yee DS et al (2009) Annexin A2 positively contributes to the malignant phenotype and secretion of IL-6 in DU145 prostate cancer cells. Int J Cancer 124:68–74PubMedCrossRefGoogle Scholar
  10. 10.
    Diaz VM, Hurtado M, Thomson TM et al (2004) Specific interaction of tissue-type plasminogen activator (t-PA) with annexin II on the membrane of pancreatic cancer cells activates plasminogen and promotes invasion in vitro. Gut 53:993–1000PubMedCrossRefGoogle Scholar
  11. 11.
    Shiozawa Y, Havens AM, Jung Y et al (2008) Annexin II/annexin II receptor axis regulates adhesion, migration, homing, and growth of prostate cancer. J Cell Biochem 105:370–380PubMedCrossRefGoogle Scholar
  12. 12.
    Tressler RJ, Updyke TV, Yeatman T et al (1993) Extracellular annexin II is associated with divalent cation-dependent tumor cell-endothelial cell adhesion of metastatic RAW117 large-cell lymphoma cells. J Cell Biochem 53:265–276PubMedCrossRefGoogle Scholar
  13. 13.
    Gerke V, Moss SE (2002) Annexins: from structure to function. Physiol Rev 82:331–371PubMedGoogle Scholar
  14. 14.
    Mussunoor S, Murray GI (2008) The role of annexins in tumour development and progression. J Pathol 216:131–140PubMedCrossRefGoogle Scholar
  15. 15.
    Yan X, Yin J, Yao H et al (2010) Increased expression of annexin A3 is a mechanism of platinum resistance in ovarian cancer. Cancer Res 70:1616–1624PubMedCrossRefGoogle Scholar
  16. 16.
    Kim A, Serada S, Enomoto T et al (2010) Targeting annexin A4 to counteract chemoresistance in clear cell carcinoma of the ovary. Expert Opin Ther Targets 14:963–971PubMedCrossRefGoogle Scholar
  17. 17.
    Song J, Shih Ie M, Chan DW et al (2009) Suppression of annexin A11 in ovarian cancer: implications in chemoresistance. Neoplasia 11:605–614PubMedGoogle Scholar
  18. 18.
    Chuthapisith S, Bean BE, Cowley G et al (2009) Annexins in human breast cancer: possible predictors of pathological response to neoadjuvant chemotherapy. Eur J Cancer 45:1274–1281PubMedCrossRefGoogle Scholar
  19. 19.
    Huebner K, Cannizzaro LA, Frey AZ et al (1988) Chromosomal localization of the human genes for lipocortin I and lipocortin II. Oncogene Res 2:299–310PubMedGoogle Scholar
  20. 20.
    Rhiem K, Klein A, Münch M et al (2003) Chromosomal region 15q21.1 is a frequent target of allelic imbalance in advanced breast carcinomas. Int J Cancer 106:74–77PubMedCrossRefGoogle Scholar
  21. 21.
    Waisman DM (1995) Annexin II tetramer: structure and function. Mol Cell Biochem 149:301–322PubMedCrossRefGoogle Scholar
  22. 22.
    Deora AB, Kreitzer G, Jacovina AT et al (2004) An annexin 2 phosphorylation switch mediates p11-dependent translocation of annexin 2 to the cell surface. J Biol Chem 279:43411–43418PubMedCrossRefGoogle Scholar
  23. 23.
    Bellagamba C, Hubaishy I, Bjorge JD et al (1997) Tyrosine phosphorylation of annexin II tetramer is stimulated by membrane binding. J Biol Chem 272:3195–3199PubMedCrossRefGoogle Scholar
  24. 24.
    McCready J, Sims JD, Chan D et al (2010) Secretion of extracellular hsp90alpha via exosomes increases cancer cell motility: a role for plasminogen activation. BMC Cancer 10:294PubMedCrossRefGoogle Scholar
  25. 25.
    Lei H, Romeo G, Kazlauskas A (2004) Heat shock protein 90{alpha}-Dependent translocation of annexin II to the surface of endothelial cells modulates plasmin activity in the diabetic rat aorta. Circ Res 94:902–909PubMedCrossRefGoogle Scholar
  26. 26.
    Oliferenko S, Paiha K, Harder T et al (1999) Analysis of CD44-containing lipid rafts: recruitment of annexin II and stabilization by the actin cytoskeleton. J Cell Biol 146:843–854PubMedCrossRefGoogle Scholar
  27. 27.
    Schnitzer JE, Liu J, Oh P (1995) Endothelial caveolae have the molecular transport machinery for vesicle budding, docking, and fusion including VAMP, NSF, SNAP, annexins, and GTPases. J Biol Chem 270:14399–14404PubMedCrossRefGoogle Scholar
  28. 28.
    Kapoor M, Zhou Q, Otero F et al (2008) Evidence for annexin II-S100A10 complex and plasmin in mobilization of cytokine activity of human TrpRS. J Biol Chem 283:2070–2077PubMedCrossRefGoogle Scholar
  29. 29.
    Ohno Y, Izumi M, Kawamura T et al (2009) Annexin II represents metastatic potential in clear-cell renal cell carcinoma. Br J Cancer 101:287–294PubMedCrossRefGoogle Scholar
  30. 30.
    Duncan R, Carpenter B, Main LC et al (2008) Characterisation and protein expression profiling of annexins in colorectal cancer. Br J Cancer 98:426–433PubMedCrossRefGoogle Scholar
  31. 31.
    Domoto T, Miyama Y, Suzuki H et al (2007) Evaluation of S100A10, annexin II and B-FABP expression as markers for renal cell carcinoma. Cancer Sci 98:77–82PubMedCrossRefGoogle Scholar
  32. 32.
    Zheng L, Huang L, Mo G et al. (2009) Characterization of a new candidate target for pancreatic cancer immunotherapy: Tyrosine phosphorylation regulates cell surface translocation of annexin A2 and contributes to pancreatic cancer invasion. In:Proceedings of the 100th Annual Meeting of the American Association for Cancer Research Denver,Colorado, USA Abstract #: 713.Google Scholar
  33. 33.
    Reeves SA, Chavez-Kappel C, Davis R et al (1992) Developmental regulation of annexin II (Lipocortin 2) in human brain and expression in high grade glioma. Cancer Res 52:6871–6876PubMedGoogle Scholar
  34. 34.
    Yeatman TJ, Updyke TV, Kaetzel MA et al (1993) Expression of annexins on the surfaces of non-metastatic and metastatic human and rodent tumor cells. Clin Exp Metastasis 11:37–44PubMedCrossRefGoogle Scholar
  35. 35.
    Chetcuti A, Margan SH, Russell P et al (2001) Loss of annexin II heavy and light chains in prostate cancer and its precursors. Cancer Res 61:6331–6334PubMedGoogle Scholar
  36. 36.
    Liu JW, Shen JJ, Tanzillo-Swarts A et al (2003) Annexin II expression is reduced or lost in prostate cancer cells and its re-expression inhibits prostate cancer cell migration. Oncogene 22:1475–1485PubMedCrossRefGoogle Scholar
  37. 37.
    Xin W, Rhodes DR, Ingold C et al (2003) Dysregulation of the annexin family protein family is associated with prostate cancer progression. Am J Pathol 162:255–261PubMedCrossRefGoogle Scholar
  38. 38.
    Yee DS, Narula N, Ramzy I et al (2007) Reduced annexin II protein expression in high-grade prostatic intraepithelial neoplasia and prostate cancer. Arch Pathol Lab Med 131:902–908PubMedGoogle Scholar
  39. 39.
    Banerjee A, Liu J, Yuan Y et al (2003) Expression of biomarkers modulating prostate cancer angiogenesis: differential expression of annexin II in prostate carcinomas from India and USA. Mol Cancer 2:34PubMedCrossRefGoogle Scholar
  40. 40.
    Wu W, Tang X, Hu W et al (2002) Identification and validation of metastasis-associated proteins in head and neck cancer cell lines by two-dimensional electrophoresis and mass spectrometry. Clin Exp Metastasis 19:319–326PubMedCrossRefGoogle Scholar
  41. 41.
    Pena-Alonso E, Rodrigo JP, Parra IC et al (2008) Annexin A2 localizes to the basal epithelial layer and is down-regulated in dysplasia and head and neck squamous cell carcinoma. Cancer Lett 263:89–98PubMedCrossRefGoogle Scholar
  42. 42.
    Karimi-Busheri F, Marcoux Y, Tredget EE et al (2002) Expression of a releasable form of annexin II by human keratinocytes. J Cell Biochem 86:737–747PubMedCrossRefGoogle Scholar
  43. 43.
    Davis RG, Vishwanatha JK (1995) Detection of secreted and intracellular annexin II by a radioimmunoassay. J Immunol Methods 188:91–95PubMedCrossRefGoogle Scholar
  44. 44.
    Zhao WQ, Chen GH, Chen H et al (2003) Secretion of annexin II via activation of insulin receptor and insulin-like growth factor receptor. J Biol Chem 278:4205–4215PubMedCrossRefGoogle Scholar
  45. 45.
    Ji NY, Park MY, Kang YH et al (2009) Evaluation of annexin II as a potential serum marker for hepatocellular carcinoma using a developed sandwich ELISA method. Int J Mol Med 24:765–771PubMedGoogle Scholar
  46. 46.
    Yan GR, Ding W, Xu SH et al. (2010) Characterization of Phosphoproteins in Gastric Cancer Secretome. OMICS.Google Scholar
  47. 47.
    Zhang J, Guo B, Zhang Y et al (2010) Silencing of the annexin II gene down-regulates the levels of S100A10, c-Myc, and plasmin and inhibits breast cancer cell proliferation and invasion. Saudi Med J 31:374–381PubMedGoogle Scholar
  48. 48.
    Puisieux A, Ji J, Ozturk M (1996) Annexin II up-regulates cellular levels of p11 protein by a post-translational mechanisms. Biochem J 313:51–55PubMedGoogle Scholar
  49. 49.
    Orend G, Chiquet-Ehrismann R (2006) Tenascin-C induced signaling in cancer. Cancer Lett 244:143–163PubMedCrossRefGoogle Scholar
  50. 50.
    Esposito I, Penzel R, Chaib-Harrireche M et al (2006) Tenascin C and annexin II expression in the process of pancreatic carcinogenesis. J Pathol 208:673–685PubMedCrossRefGoogle Scholar
  51. 51.
    Chung C, Murphy-Ullrich J, Erickson H (1996) Mitogenesis, cell migration, and loss of focal adhesions induced by tenascin-C interacting with its cell surface receptor, annexin II. Mol Biol Cell 7:883–892PubMedGoogle Scholar
  52. 52.
    Wilson KE, Bartlett JMS, Miller EP et al (1999) Regulation and function of the extracellular matrix protein tenascin-C in ovarian cancer cell lines. Br J Cancer 80:685–692PubMedCrossRefGoogle Scholar
  53. 53.
    Mai J, Finley RL Jr, Waisman DM et al (2000) Human procathepsin B interacts with the annexin II tetramer on the surface of tumor cells. J Biol Chem 275:12806–12812PubMedCrossRefGoogle Scholar
  54. 54.
    Cavallo-Medved D, Rudy D, Blum G et al (2009) Live-cell imaging demonstrates extracellular matrix degradation in association with active cathepsin B in caveolae of endothelial cells during tube formation. Exp Cell Res 315:1234–1246PubMedCrossRefGoogle Scholar
  55. 55.
    Lu G, Maeda H, Reddy SV et al (2006) Cloning and characterization of the annexin II receptor on human marrow stromal cells. J Biol Chem 281:30542–30550PubMedCrossRefGoogle Scholar
  56. 56.
    Wirl G, Schwartz-Albiez R (1990) Collagen-binding proteins of mammary epithelial cells are related to Ca2(+)- and phospholipid-binding annexins. J Cell Physiol 144:511–522PubMedCrossRefGoogle Scholar
  57. 57.
    Das S, Shetty P, Valapala M et al (2010) Signal transducer and activator of transcription 6 (STAT6) is a novel interactor of annexin A2 in prostate cancer cells. Biochemistry 49:2216–2226PubMedCrossRefGoogle Scholar
  58. 58.
    Singh P, Wu H, Clark C et al (2007) Annexin II binds progastrin and gastrin-like peptides, and mediates growth factor effects of autocrine and exogenous gastrins on colon cancer and intestinal epithelial cells. Oncogene 26:425–440PubMedCrossRefGoogle Scholar
  59. 59.
    Singh P (2007) Role of annexin-II in GI cancers: interaction with gastrins/progastrins. Cancer Lett 252:19–35PubMedCrossRefGoogle Scholar
  60. 60.
    Semov A, Moreno MJ, Onichtchenko A et al (2005) Metastasis-associated protein S100A4 induces angiogenesis through interaction with annexin II and accelerated plasmin formation. J Biol Chem 280:20833–20841PubMedCrossRefGoogle Scholar
  61. 61.
    Nedjadi T, Kitteringham N, Campbell F et al (2009) S100A6 binds to annexin 2 in pancreatic cancer cells and promotes pancreatic cancer cell motility. Br J Cancer 101:1145–1154PubMedCrossRefGoogle Scholar
  62. 62.
    Kwaan HC (1992) The plasminogen-plasmin system in malignancy. Cancer Metastasis Rev 11:291–311PubMedCrossRefGoogle Scholar
  63. 63.
    Sharma MC, Sharma M (2007) The role of annexin II in angiogenesis and tumor progression: a potential therapeutic target. Curr Pharm Des 13:3568–3575PubMedCrossRefGoogle Scholar
  64. 64.
    Kassam G, Le BH, Choi KS et al (1998) The p11 subunit of the annexin II tetramer plays a key role in the stimulation of t-PA-dependent plasminogen activation. Biochemistry 37:16958–16966PubMedCrossRefGoogle Scholar
  65. 65.
    Hajjar KA, Jacovina AT, Chacko J (1994) An endothelial cell receptor for plasminogen/tissue plasminogen activator. I. Identity with annexin II. J Biol Chem 269:21191–21197PubMedGoogle Scholar
  66. 66.
    Sharma M, Ownbey RT, Sharma MC (2010) Breast cancer cell surface annexin II induces cell migration and neoangiogenesis via tPA dependent plasmin generation. Exp Mol Pathol 88:278–286PubMedCrossRefGoogle Scholar
  67. 67.
    Coghlin C, Murray GI (2010) Current and emerging concepts in tumour metastasis. J Pathol 222:1–15PubMedCrossRefGoogle Scholar
  68. 68.
    Paciucci R, Tora M, Diaz VM et al (1998) The plasminogen activator system in pancreas cancer: role of t-PA in the invasive potential in vitro. Oncogene 16:625–633PubMedCrossRefGoogle Scholar
  69. 69.
    Roda O, Valero ML, Peiro S et al (2003) New insights into the tPA-Annexin A2 interaction. Is annexin A2 CYS8 the sole requirement for this association? J Biol Chem 278:5702–5709PubMedCrossRefGoogle Scholar
  70. 70.
    Zhang X, Zhou H, Wang J et al (2002) Arsenic trioxide, retinoic acid and Ara-c regulated the expression of annexin II on the surface of APL cells, a novel co-receptor for plasminogen/tissue plasminogen activator. Thromb Res 106:63–70PubMedCrossRefGoogle Scholar
  71. 71.
    Bao H, Jiang M, Zhu M et al (2009) Overexpression of Annexin II affects the proliferation, apoptosis, invasion and production of proangiogenic factors in multiple myeloma. Int J Hematol 90:177–185PubMedCrossRefGoogle Scholar
  72. 72.
    Gillette JM, Chan DC, Nielsen-Preiss SM (2004) Annexin 2 expression is reduced in human osteosarcoma metastases. J Cell Biochem 92:820–832PubMedCrossRefGoogle Scholar
  73. 73.
    Jung Y, Wang J, Song J et al (2007) Annexin II expressed by osteoblasts and endothelial cells regulates stem cell adhesion, homing, and engraftment following transplantation. Blood 110:82–90PubMedCrossRefGoogle Scholar
  74. 74.
    Hayes MJ, Shao D, Bailly M et al (2006) Regulation of actin dynamics by annexin 2. EMBO J 25:1816–1826PubMedCrossRefGoogle Scholar
  75. 75.
    Thiel C, Osborn M, Gerke V (1992) The tight association of the tyrosine kinase substrate annexin II with the submembranous cytoskeleton depends on intact p11- and Ca(2+)-binding sites. J Cell Sci 103:733–742PubMedGoogle Scholar
  76. 76.
    Pu Z, Wei Z, Juan T et al (2009) Annexin II promotes invasion and migration of human hepatocellular carcinoma cells in vitro via its interaction with HAb18G/CD147. Cancer Sci 101:387–395Google Scholar
  77. 77.
    Tatenhorst L, Rescher U, Gerke V et al (2006) Knockdown of annexin 2 decreases migration of human glioma cells in vitro. Neuropathol Appl Neurobiol 32:271–277PubMedCrossRefGoogle Scholar
  78. 78.
    Hou Y, Yang L, Mou M et al (2008) Annexin A2 regulates the levels of plasmin, S100A10 and fascin in L5178Y cells. Cancer Investig 26:809–815CrossRefGoogle Scholar
  79. 79.
    Chen J, He QY, Yuen AP et al (2004) Proteomics of buccal squamous cell carcinoma: the involvement of multiple pathways in tumorigenesis. Proteomics 4:2465–2475PubMedCrossRefGoogle Scholar
  80. 80.
    Tomonaga T, Matsushita K, Yamaguchi S et al (2004) Identification of altered protein expression and post-translational modifications in primary colorectal cancer by using agarose two-dimensional gel electrophoresis. Clin Cancer Res 10:2007–2014PubMedCrossRefGoogle Scholar
  81. 81.
    Takano S, Togawa A, Yoshitomi H et al (2008) Annexin II overexpression predicts rapid recurrence after surgery in pancreatic cancer patients undergoing gemcitabine-adjuvant chemotherapy. Ann Surg Oncol 15:3157–3168PubMedCrossRefGoogle Scholar
  82. 82.
    Eustace AJ, Dowling P, Henry M et al. (2011) 2D-DIGE analysis of phospho-enriched fractions from dasatinib-treated melanoma cell lines. J Proteomics.Google Scholar
  83. 83.
    Laumonnier Y, Syrovets T, Burysek L et al (2006) Identification of the annexin A2 heterotetramer as a receptor for the plasmin-induced signaling in human peripheral monocytes. Blood 107:3342–3349PubMedCrossRefGoogle Scholar
  84. 84.
    He KL, Sui G, Xiong H et al. (2010) Feedback regulation of endothelial cell surface plasmin generation by PKC dependent phosphorylation of annexin A2. J Biol Chem.Google Scholar
  85. 85.
    Tsunezumi J, Yamamoto K, Higashi S et al (2008) Matrilysin (matrix metalloprotease-7) cleaves membrane-bound annexin II and enhances binding of tissue-type plasminogen activator to cancer cell surfaces. FEBS J 275:4810–4823PubMedCrossRefGoogle Scholar
  86. 86.
    Wang CY, Lin YS, Su WC et al (2009) Glycogen synthase kinase-3 and omi/HtrA2 induce annexin A2 cleavage followed by cell cycle inhibition and apoptosis. Mol Biol Cell 20:4153–4161PubMedCrossRefGoogle Scholar
  87. 87.
    Wang H, Kachman MT, Schwartz DR et al (2004) Comprehensive proteome analysis of ovarian cancers using liquid phase separation, mass mapping and tandem mass spectrometry: a strategy for identification of candidate cancer biomarkers. Proteomics 4:2476–2495PubMedCrossRefGoogle Scholar
  88. 88.
    Gagne JP, Ethier C, Gagne P et al (2007) Comparative proteome analysis of human epithelial ovarian cancer. Proteome Sci 5:16PubMedCrossRefGoogle Scholar
  89. 89.
    Tchagang AB, Tewfik AH, DeRycke MS et al (2008) Early detection of ovarian cancer using group biomarkers. Mol Cancer Ther 7:27–37PubMedCrossRefGoogle Scholar
  90. 90.
    Gunawardana CG, Kuk C, Smith CR et al (2009) Comprehensive analysis of conditioned media from ovarian cancer cell lines identifies novel candidate markers of epithelial ovarian cancer. J Proteome Res 8:4705–4713PubMedCrossRefGoogle Scholar
  91. 91.
    Faca VM, Ventura AP, Fitzgibbon MP et al (2008) Proteomic analysis of ovarian cancer cells reveals dynamic processes of protein secretion and shedding of extra-cellular domains. PLoS ONE 3:e2425PubMedCrossRefGoogle Scholar
  92. 92.
    Ween MP, Lokman NA, Hoffmann P et al. (2010) Transforming growth factor-beta-induced protein secreted by peritoneal cells increases the metastatic potential of ovarian cancer cells. Int J Cancer.Google Scholar
  93. 93.
    Sharma MR, Rothman V, Tuszynski GP et al (2006) Antibody-directed targeting of angiostatin’s receptor annexin II inhibits Lewis Lung Carcinoma tumor growth via blocking of plasminogen activation: Possible biochemical mechanism of angiostatin’s action. Exp Mol Pathol 81:136–145PubMedCrossRefGoogle Scholar
  94. 94.
    Jacovina AT, Zhong F, Khazanova E et al (2001) Neuritogenesis and the nerve growth factor-induced differentiation of PC-12 cells requires annexin II-mediated plasmin generation. J Biol Chem 276:49350–49358PubMedCrossRefGoogle Scholar
  95. 95.
    Tuszynski GP, Sharma MR, Rothman VL et al (2002) Angiostatin binds to tyrosine kinase substrate annexin II through the lysine-binding domain in endothelial cells. Microvasc Res 64:448–462PubMedCrossRefGoogle Scholar
  96. 96.
    Braden AR, Kafka MT, Cunningham L et al (2009) Polymeric nanoparticles for sustained down-regulation of annexin A2 inhibit prostate tumor growth. J Nanosci Nanotechnol 9:2856–2865PubMedCrossRefGoogle Scholar
  97. 97.
    Kesavan K, Ratliff J, Johnson EW et al (2010) Annexin A2 is a molecular target for TM601, a peptide with tumor-targeting and anti-angiogenic effects. J Biol Chem 285:4366–4374PubMedCrossRefGoogle Scholar
  98. 98.
    Qi YJ, He QY, Ma YF et al (2008) Proteomic identification of malignant transformation-related proteins in esophageal squamous cell carcinoma. J Cell Biochem 104:1625–1635PubMedCrossRefGoogle Scholar
  99. 99.
    Syed SP, Martin AM, Haupt HM et al (2007) Angiostatin receptor annexin II in vascular tumors including angiosarcoma. Hum Pathol 38:508–513PubMedCrossRefGoogle Scholar
  100. 100.
    Emoto K, Yamada Y, Sawada H et al (2001) Annexin II overexpression correlates with stromal tenascin-C overexpression. Cancer 92:1419–1426PubMedCrossRefGoogle Scholar
  101. 101.
    Nygaard SJ, Haugland HK, Kristoffersen EK et al (1998) Expression of annexin II in glioma cell lines and in brain tumor biopsies. J Neurooncol 38:11–18PubMedCrossRefGoogle Scholar
  102. 102.
    Roseman BJ, Bollen A, Hsu J et al (1994) Annexin II marks astrocytic brain tumors of high histologic grade. Oncol Res 6:561–567PubMedGoogle Scholar
  103. 103.
    Zhong LP, Wei KJ, Yang X et al (2009) Increased expression of annexin A2 in oral squamous cell carcinoma. Arch Oral Biol 54:17–25PubMedCrossRefGoogle Scholar
  104. 104.
    Hellman K, Alaiya AA, Becker S et al (2009) Differential tissue-specific protein markers of vaginal carcinoma. Br J Cancer 100:1303–1314PubMedCrossRefGoogle Scholar
  105. 105.
    Bae SM, Lee CH, Cho YL et al (2005) Two-dimensional gel analysis of protein expression profile in squamous cervical cancer patients. Gynecol Oncol 99:26–35PubMedCrossRefGoogle Scholar
  106. 106.
    Olwill SA, McGlynn H, Gilmore WS et al (2005) Annexin II cell surface and mRNA expression in human acute myeloid leukaemia cell lines. Thromb Res 115:109–114PubMedCrossRefGoogle Scholar
  107. 107.
    Zhang F, Zhang L, Zhang B et al (2009) Anxa2 plays a critical role in enhanced invasiveness of the multidrug resistant human breast cancer cells. J Proteome Res 8:5041–5047PubMedCrossRefGoogle Scholar
  108. 108.
    Rescher U, Ludwig C, Konietzko V et al (2008) Tyrosine phosphorylation of annexin A2 regulates Rho-mediated actin rearrangement and cell adhesion. J Cell Sci 121:2177–2185PubMedCrossRefGoogle Scholar
  109. 109.
    Huang Y, Jin Y, Yan CH et al (2008) Involvement of annexin A2 in p53 induced apoptosis in lung cancer. Mol Cell Biochem 309:117–123PubMedCrossRefGoogle Scholar
  110. 110.
    Masaki T, Tokuda M, Fujimura T et al (1994) Involvement of annexin I and annexin II in hepatocyte proliferation: can annexins I and II be markers for proliferative hepatocytes? Hepatology 20:425–435PubMedCrossRefGoogle Scholar
  111. 111.
    Zimmermann U, Woenckhaus C, Pietschmann S et al (2004) Expression of annexin II in conventional renal cell carcinoma is correlated with Fuhrman grade and clinical outcome. Virchows Arch 445:368–374PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2011

Authors and Affiliations

  • Noor A. Lokman
    • 1
  • Miranda P. Ween
    • 1
  • Martin K. Oehler
    • 1
    • 2
  • Carmela Ricciardelli
    • 1
  1. 1.Discipline of Obstetrics and Gynaecology, School of Paediatrics and Reproductive Health, Research Centre for Reproductive Health, Robinson InstituteUniversity of AdelaideAdelaideAustralia
  2. 2.Department of Gynaecological OncologyRoyal Adelaide HospitalAdelaideAustralia

Personalised recommendations