RGD Reference Report - Anti-tumor effect of endostatin mediated by retroviral gene transfer in mice bearing renal cell carcinoma. - Rat Genome Database

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

Authors: Coutinho, EL  Andrade, LN  Chammas, R  Morganti, L  Schor, N  Bellini, MH 
Citation: Coutinho EL, etal., FASEB J. 2007 Oct;21(12):3153-61. Epub 2007 May 18.
RGD ID: 2293308
Pubmed: PMID:17513560   (View Abstract at PubMed)
DOI: DOI:10.1096/fj.07-8412com   (Journal Full-text)

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 mm3, while the tumor volume of control was 234.5 +/- 14.8 mm3. Microvascular density was significantly decreased on treatment (control 9.79 vs. ES 2.53%, <0.001) accompanied by a 23-fold increase in intratumoral 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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
renal cell carcinoma  IEP 2293308 RGD 
renal cell carcinoma  ISOCASP3 (Homo sapiens)2293308; 2293308 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Casp3  (caspase 3)

Genes (Mus musculus)
Casp3  (caspase 3)

Genes (Homo sapiens)
CASP3  (caspase 3)


Additional Information