Anti-tumor effect of endostatin mediated by retroviral gene transfer in mice bearing renal cell carcinoma

Anti-tumor effect of endostatin mediated by retroviral gene transfer in mice bearing renal cell carcinoma

Author Coutinho, Enia Lucia Autor UNIFESP Google Scholar
Andrade, Luciana Nogueira de Sousa Google Scholar
Chammas, Roger Google Scholar
Morganti, Ligia Google Scholar
Schor, Nestor Autor UNIFESP Google Scholar
Bellini, Maria Helena Autor UNIFESP Google Scholar
Institution IPEN CNEN SP
Universidade Federal de São Paulo (UNIFESP)
Universidade de São Paulo (USP)
Abstract We investigated whether transfer of the gene encoding the angiogenesis inhibitor endostatin into the NIH/3T3 fibroblast cell line could inhibit renal tumor growth in vivo. NIH/3T3 cells were transduced with retroviral vectors containing the murine endostatin (ES) gene. SCID mice bearing CaKi-1 derived tumors were given a subcutaneous injection of either ES-transduced cells or control cells and were monitored for tumor growth. At the end of the in vivo experiment, the mean tumor volume of treated mice was 51.6 +/- 2.4 mm(3), while the tumor volume of control was 234.5 +/- 14.8 mm(3). Microvascular density was significantly decreased on treatment (control 9.79 vs. ES 2.53%, < 0.001) accompanied by a 23-fold increase in intraturmoral necrotic area and a 2.94-fold increase in the apoptotic index, determined by immunohistochemistry with anti- activated caspase-3. Apoptotic cells were found in foci enriched in infiltrating leukocytes. in conclusion, retroviral endostatin gene transfer led to secretion of functional endostatin that was sufficiently active to inhibit tumor angiogenesis and tumor growth. A second mechanism may also be implied in endostatin-dependent tumor regression, associated with tumor infiltration of leukocytes. Besides its antiangiogenic properties, endostatin may be a promising adjuvant to immunotherapy.
Keywords gene therapy
Language English
Date 2007-10-01
Published in Faseb Journal. Bethesda: Federation Amer Soc Exp Biol, v. 21, n. 12, p. 3153-3161, 2007.
ISSN 0892-6638 (Sherpa/Romeo, impact factor)
Publisher Federation Amer Soc Exp Biol
Extent 3153-3161
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000249781600016

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