Angiogenesis in the development of papillomas and carcinomas in the mouse two stage model

BOLONTRADE, MARCELA F.; LARCHER, FERNANDO; STERN, MARIANA C.; RODRÍGUEZ PUEBLO, MARCELO; JORCANO, JOSÉ L.; GIMENEZ CONTI, IRMA B.; CONTI, CLAUDIO J.

San Diego, California

Simposio; 88vo Encuentro Anual. American Association for Cancer Research (AACR); 1997

American Association for Cancer Research (AACR)

Several studies have shown that angiogenesis is essential for tumor development; however, its pattern has not been extensively studied in the mouse skin carcinogenesis model. Since VEGF/VPF is a specific mitogen of endothelial cells overexpressed in several human and experimental tumors, and we have previously shown that is expressed in response to TPA and Ras activation, we studied its expression in lesions induced by DMBA and TPA in SENCAR mice, both by immunohistochemistry and by western blot. Also to study its role in papilloma progression, we studied two strains with different susceptibility to progression (SSIN and SENCAR B/Pt). The results showed that VEGF/VPF is expressed in both papillomas and carcinomas; however, no marked difference was observed between the early and the late lesions. Using a marker of endothelial cells (anti-CD31 mAb) to assess the vascular density, we observed not only an increase in density of blood vessels but also a change in their morphology. These results showed the importance of angiogenesis in the formation of papillomas and subsequent progression to malignancy and indicate that VEGF and probably other angiogenic factors play a role in this model.