Exp Mol Med.  2008 Apr;40(2):196-207. 10.3858/emm.2008.40.2.196.

T-CAM, a fastatin-FIII 9-10 fusion protein, potently enhances anti-angiogenic and anti-tumor activity via alphavbeta3 and alpha5beta1 integrins

Affiliations
  • 1Cell and Matrix Research Institute, Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Daegu 700-422, Korea. iskim@knu.ac.kr

Abstract

We made fusion protein of fastatin and FIII 9-10, termed tetra-cell adhesion molecule (T-CAM) that can interact simultaneously with alphavbeta3 and alpha5beta1 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 alphavbeta3 and alpha5beta1 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.

Keyword

angiogenesis inhibitors; angiostatic proteins; antineoplastic agents; cell adhesion molecules; integrin alphavbeta3; integrin alpha5beta1
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