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

• Nam JO
• Jung MY
• Thapa N
• Lee BH
• Park RW
• Kim IS

• KMID: 1052942
• DOI: http://doi.org/10.3858/emm.2008.40.2.196

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

MeSH Terms

Angiogenesis Inhibitors/chemistry/*pharmacology
Animals
Antineoplastic Agents/chemistry/*pharmacology
Base Sequence
Benzocaine/chemistry/*pharmacology
Cell Line, Tumor
Cell Movement
Cell Proliferation
Cells, Cultured
Chloramphenicol/chemistry/*pharmacology
DNA Primers
Drug Combinations
Factor VIII/chemistry/*pharmacology
Humans
Integrin alpha5beta1/*physiology
Integrin alphaVbeta3/*physiology
Male
Mice
Mice, Inbred BALB C
Nitrofurazone/chemistry/*pharmacology
Recombinant Fusion Proteins/chemistry/*pharmacology