T-CAM, a fastatin-FIII 9-10 fusion protein, potently enhances anti-angiogenic and anti-tumor activity via alphavbeta3 and alpha5beta1 integrins.
10.3858/emm.2008.40.2.196
- Author:
Ju Ock NAM
1
;
Mi Yeon JUNG
;
Narendra THAPA
;
Byung Heon LEE
;
Rang Woon PARK
;
In San KIM
Author Information
1. Cell and Matrix Research Institute, Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Daegu 700-422, Korea. iskim@knu.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
angiogenesis inhibitors;
angiostatic proteins;
antineoplastic agents;
cell adhesion molecules;
integrin alphavbeta3;
integrin alpha5beta1
- MeSH:
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
- From:Experimental & Molecular Medicine
2008;40(2):196-207
- CountryRepublic of Korea
- Language:English
-
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.
