Annexin II-Mediated Ca++ Influx Regulates Endothelial Cell (EC) Apoptosis and Tumor Angiogenesis
Final rept. 15 Sep 2003-14 Sep 2005
DREXEL UNIV PHILADELPHIA PA
Pagination or Media Count:
Angiostatin AS the first four kringle domain K1-4 of plasminogen PLG, blocks angiogenesis and breast cancer progression almost 95 in xenograft model. Despite great therapeutic potential in breast cancer its mechanism of action is unclear. We previously reported that AS ligand binds to endothelial cell surface annexin II and blocks PLG bindings. Emerging role of annexin II in cancer prompted us to investigate its possible mechanism in breast cancer. In this study we report that annexin II gene and protein abundantly expressed in highly invasive and metastatic breast cancer cells MDA-MB231 but not in non invasive MCF-7 cells. Annexin II expression is regulated by proangiogenic growth factors. Growth factors also phophorylate tyrosine residue of annexin II in MDA-MB231 cells indicating the involvement of signal transduction mechanism. MDA-MB231 cells activated PLG to plasm in PL in time dependent manner whereas MCF-7 cells lacking annexin II expression failed to activate PLG indicating that MDA-MB231 cells require annexin II for PLG activation and may be involved in invasion and migration. Our data indicates that MDA-MB231 cells induced invasion through ECM in PLG dependent manner but MCF-7 failed to invade and migrate suggesting specific role of annexin II mediated PL generation in invasion and migration. It is possible to block breast cancer invasion and migration by blocking annexin II and may be an attractive target.
- Medicine and Medical Research