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KMID : 0620920080400020196
Experimental & Molecular Medicine
2008 Volume.40 No. 2 p.196 ~ p.207
T-CAM, a fastatin-FIII 9-10 fusion protein, potently enhances anti-angiogenic and anti-tumor activity via ¥áv¥â3 and ¥á5¥â1 integrins
Nam Ju-Ock

Lee Byung-Heon
Kim In-San
Jung Mi-Yeon
Thapa Narendra
Park Rang-Woon
Abstract
We made fusion protein of fastatin and FIII 9-10, termed tetra-cell adhesion molecule (T-CAM) that can interact simultaneously with ¥á v¥â 3 and ¥á 5¥â 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 ¥á v¥â 3 and ¥á 5¥â 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.
KEYWORD
angiogenesis inhibitors, angiostatic proteins, antineoplastic agents, cell adhesion molecules, integrin ¥á v¥â 3, integrin ¥á 5¥â 1
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