T-CAM, a fastatin-FIII 9-10 fusion protein, potently enhances anti-angiogenic and anti-tumor activity via alphavbeta3 and alpha5beta1 integrins.
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.
Nam
Ju-Ock
JO
Cell and Matrix Research Institute, Department of Biochemistry and Cell Biology, School of Medicine, Kyungpook National University, Daegu 700-422, Korea.
Jung
Mi-Yeon
MY
Thapa
Narendra
N
Lee
Byung-Heon
BH
Park
Rang-Woon
RW
Kim
In-San
IS
D020533:Angiogenesis Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D001483:Base Sequence; D001566:Benzocaine / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D002701:Chloramphenicol / Q000737:chemistry / Q000494:pharmacology*; D017931:DNA Primers; D004338:Drug Combinations; D005169:Factor VIII / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D039081:Integrin alpha5beta1 / Q000502:physiology*; D039302:Integrin alphaVbeta3 / Q000502:physiology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009583:Nitrofurazone / Q000737:chemistry / Q000494:pharmacology*; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000494:pharmacology*
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D017931:DNA Primers; D004338:Drug Combinations; D039081:Integrin alpha5beta1; D039302:Integrin alphaVbeta3; D011993:Recombinant Fusion Proteins; C013989:fastins; D002701:Chloramphenicol; D005169:Factor VIII; D001566:Benzocaine; D009583:Nitrofurazone