1.T-CAM, a fastatin-FIII 9-10 fusion protein, potently enhances anti-angiogenic and anti-tumor activity via alphavbeta3 and alpha5beta1 integrins.
Ju Ock NAM ; Mi Yeon JUNG ; Narendra THAPA ; Byung Heon LEE ; Rang Woon PARK ; In San KIM
Experimental & Molecular Medicine 2008;40(2):196-207
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.
Angiogenesis Inhibitors/chemistry/*pharmacology
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Animals
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Antineoplastic Agents/chemistry/*pharmacology
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Base Sequence
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Benzocaine/chemistry/*pharmacology
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Cell Line, Tumor
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Cell Movement
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Cell Proliferation
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Cells, Cultured
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Chloramphenicol/chemistry/*pharmacology
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DNA Primers
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Drug Combinations
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Factor VIII/chemistry/*pharmacology
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Humans
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Integrin alpha5beta1/*physiology
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Integrin alphaVbeta3/*physiology
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Male
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Mice
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Mice, Inbred BALB C
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Nitrofurazone/chemistry/*pharmacology
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Recombinant Fusion Proteins/chemistry/*pharmacology