Angiogenesis in the development of chemically induced tumors

BOLONTRADE MARCELA F, GIMENEZ CONTI IRMA B, CONTI CLAUDIO J

Rhodes, Greece

Conferencia; NATO Special Conference "Angiogenesis: Models, Modulators and Clinical Applications"; 1997

NATO

Angiogenesis is essential for tumor development. We have analyzed the angiogenic response induced in the two stage carcinogenesis model in SENCAR mice. The role of angiogenesis has not been extensively explored in this model, the paradigm of multistage carcinogenesis and a model for exophytic lesions. VEGF/VPF is a specific mitogen of endothelial cells over expressed in several human and experimental tumors. We have previously shown that it is expressed in response to Ras activation, a genetic consequence of initiation in this model, and here we studied its protein expression in lesions induced by chemical carcinogenesis in SENCAR mice. We also analyzed the vasculature of normal and hyperplastic skin, focal epidermal hyperplasias, papillomas at different stages and squamous cell carcinomas. We also analyzed the vascularization of papillomas induced in two strains of mice that differ in their susceptibility to progression (SSIN and SENCAR B/Pt). The results show that VEGF/VPF is expressed in both papillomas and carcinomas with no marked difference observed between the early and the late lesions. Angiogenesis is turned on in the earliest stages of papilloma formation. In late stages, regardless of state of progression, the predominant response is a change in the morphology of the vessels, evidenced by an increase in the size of the blood vessels. Thus, in the SENCAR mouse model, the angiogenesis switch is a very early event, probably related to the development of early papillomas. Therefore, the density of blood vessels cannot be used as a predictor of malignant progression in this model.