Abstract 1303: Inhibition of human breast cancer cell (MDA-MB231) migration, neoangiogensis and tumor growth by selective disruption of annexin II function: in vitro and in vivo studies

Annexin II, an abundant phospholipid binding cell surface protein, binds tissue plasminogen activator (tPA) and functions as a regulator of fibrinolysis. Annexin II also mediates angiogenesis and enhances tumor growth and metastasis. However, the mechanism supporting this role is not known. Using a human breast cancer model we found that invasive human breast cancer cells (MDA-MB231) synthesize annexin II and tPA. Annexin II interacted with tPA in vitro leading to conversion of zymogen plasminogen to the reactive enzyme plasmin. Cell surface generated plasmin inhibited the migration of MDA-MB231 cells. Silencing of the annexin II gene in mDA-MB231 cells abolished tPA binding thereby inhibiting tPA dependent plasmin generation. Moreover these annexin II suppressed MDA-MB231 cells exhibited reduced motility. Immunohistochemical analysis of prediagnosed clinical specimens showed abundant secretion of tPA and expression of annexin II on the surface of invasive cancer cells which correlates with neovascularization of the tumor. Intravenous administration of the anti-annexin II antibody to mice bearing MDA-MB231 tumors significantly inhibited tumor growth possibly due to blocked neoangiogenic activity. Taken together, these data suggest that annexin II dependent plasmin generation may be an early event switching breast cancer from the prevascular phase to the vascular phase with the possibility of metastasis. Annexin II may be an attractive target for therapeutic strategies aimed to inhibit neoangiogenesis and breast cancer metastasis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1303.