Angiostatin gene therapy inhibits the growth of murine squamous cell carcinoma in vivo.
Tumor growth is an angiogenesis-dependent process and therapeutic strategies aimed at inhibiting angiogenesis are theoretically attractive. Angiostatin has been shown to potently inhibit endothelial proliferation in vitro and tumor growth in vivo. We now show that a shift in the balance of tumor angiogenesis by gene transfer of a cDNA coding for mouse angiostatin into mouse squamous cell carcinoma NRS-1 and SCC-VII cells suppresses tumor growth in vivo. The inhibition of an angiostatin-transfected tumor was accompanied by a marked reduction in vascularity and the presence of many apoptotic tumor cells. However, transfected-angiostatin cDNA does not affect the expression of the vascular endothelial growth factor (VEGF) and VEGF-R2 in the vascular endothelium. The inhibition mechanisms of neovascularization may be mediated independent of VEGF:VEGF-R2 complex. Our data may provide a useful approach for human oral cancer therapy by gene therapy with angiostatin.
Matsumoto
G
G
First Department of Oral Surgery, Kanagawa Dental College, 82 Inaoka, Yokosuka, Kanagawa 238-8580, Japan. gmatsu@kdcnet.ac.jp
Ohmi
Y
Y
Shindo
J
J
D043168:Angiostatins; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D015152:Blotting, Northern / Q000379:methods; D015153:Blotting, Western / Q000379:methods; D002294:Carcinoma, Squamous Cell / Q000098:blood supply / Q000235:genetics / Q000628:therapy*; D018076:DNA, Complementary; D016228:Endothelial Growth Factors / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D005260:Female; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D008222:Lymphokines / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D010446:Peptide Fragments / Q000235:genetics* / Q000627:therapeutic use; D010958:Plasminogen / Q000235:genetics* / Q000627:therapeutic use; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D016133:Polymerase Chain Reaction / Q000379:methods; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D017978:Receptors, Growth Factor / Q000378:metabolism; D040262:Receptors, Vascular Endothelial Growth Factor; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D018076:DNA, Complementary; D016228:Endothelial Growth Factors; D008222:Lymphokines; D010446:Peptide Fragments; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D017978:Receptors, Growth Factor; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D043168:Angiostatins; D010958:Plasminogen; D020794:Receptor Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor