T-CAM, a fastatin-FIII 9-10 fusion protein, potently enhances anti-angiogenic and anti-tumor activity αvβ3 and α5β1 integrins

Abstract

We made fusion protein of fastatin and FIII 9-10, termed tetra-cell adhesion molecule (T-CAM) that can interact simultaneously with α vβ 3 and α 5β 1 integrins, both playing important roles in tumor angiogenesis. T-CAM can serve as a cell adhesion substrate mediating adhesion and migration of endothelial cells in α vβ 3 and α 5β 1 integrin-dependent manner. T-CAM showed pronounced anti-angiogenic activities such as inhibition of endothelial cell tube formation, endothelial cell proliferation, and induction of endothelial cell apoptosis. T-CAM also inhibited angiogenesis and tumor growth in mouse xenograft model. The anti-angiogenic and anti-tumoral activity of molecule like fastatin could be improved by fusing it with integrin-recognizing cell adhesion domain from other distinct proteins. The strategy of combining two distinct anti-angiogenic molecules or cell adhesion domains could facilitate designing improved anticancer agent of therapeutic value.

TGFBI Expression Predicts the Survival of Patients With Oropharyngeal Squamous Cell Carcinoma

“…On the contrary, Wen et al (19) have reported that TGFBI acts as a tumor suppressor through the Akt/mTOR pathway. Son et al (25) and Nam et al (26) have suggested that TGFBI has anti-angiogenic and anti-tumor effects.…”