Expression of angiostatin cDNA in a murine renal cell carcinoma suppresses tumor growth in vivo.
OBJECTIVE
To investigate the effectiveness of angiostatin gene therapy for renal cancer using a mouse model. The generally poor prognosis of advanced renal cancer indicates the need for new therapeutic modalities. The dependency of solid tumor growth on angiogenesis suggests that antiangiogenic therapy would be effective against renal cell carcinoma, which is generally a hypervascular tumor.


METHODS
Murine renal cancer cells (Renca) transfected with murine angiostatin cDNA (AST-Renca) were subcutaneously implanted in BALB/c mice. Subsequently, the macroscopic appearance and volume of tumors were evaluated once per week. Renca cells transfected with empty plasmid DNA (mock-Renca) were used as a control. In addition, histologic sections of tumor were analyzed for neovascularization on the basis of an immunohistochemical analysis for CD31. The antitumor effect of AST-Renca on a parental Renca tumor at a distant site was also evaluated.


RESULTS
The mean volume of AST-Renca tumors was significantly less than that of the control vector-transfected tumors 3 weeks after implantation. In the cell proliferation assay, the expression of angiostatin did not inhibit the proliferation of Renca cells in vitro. Immunohistochemical analysis of neovascularization by staining with anti-CD31 antibody revealed that angiostatin suppressed tumor vessel formation. Moreover, implantation of AST-Renca inhibited the growth of parental Renca implanted simultaneously at a distant site.


CONCLUSIONS
Expression of an angiostatin transgene can suppress the growth of murine renal cancer through the inhibition of tumor-induced angiogenesis. Angiostatin gene therapy may be effective against renal cancer.
Fukumori
Tomoharu
T
Department of Urology, University of Tokushima School of Medicine, Tokushima, Japan.
Nishitani
Masa aki
Ma
Naroda
Takushi
T
Onishi
Tomoichiro
T
Oka
Natsuo
N
Kanayama
Hiro omi
Ho
Kagawa
Susumu
S
D043168:Angiostatins; D000818:Animals; D002292:Carcinoma, Renal Cell / Q000098:blood supply / Q000378:metabolism / Q000628:therapy*; D018076:DNA, Complementary / Q000378:metabolism*; D015316:Genetic Therapy; D007680:Kidney Neoplasms / Q000098:blood supply / Q000378:metabolism / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D010446:Peptide Fragments / Q000235:genetics* / Q000378:metabolism; D010958:Plasminogen / Q000235:genetics* / Q000378:metabolism
D018076:DNA, Complementary; D010446:Peptide Fragments; D043168:Angiostatins; D010958:Plasminogen