Metastasis and tumor growth depend on the ability of endothelial and cancer cells to migrate to and invade target tissues. Integrins are essential for cell migration and invasion as they bind directly to the components of the extracellular matrix. Integrin α5β1 binds specifically to fibronectin and it is up-regulated on blood vessels in human tumor biopsies. We found that integrin α5β1 was expressed on certain human cancer cell lines of various origins including breast, lung, skin, and connective tissue, in addition to endothelial cells such as HUVECs. Some of these cancer cells are highly metastatic in vivo; therefore we investigated the role of integrin α5β1 in cell migration in a transwell migration system. HUVECs and cancer cells that expressed high levels of integrin α5β1 migrated towards a fibronectin gradient while cells expressing low levels of integrin α5β1 generally did not respond to fibronectin. This directional movement was inhibited in a dose-dependent manner by a chimeric anti-integrin α5β1 antibody (M200). Our results demonstrated that integrin α5β1 plays a significant role in endothelial and cancer cell migration and the activity can be blocked effectively by M200. Currently, M200 is in Phase I clinical trials as an anti-angiogenesis agent for solid tumors.
[Proc Amer Assoc Cancer Res, Volume 45, 2004]