Angiogenesis as an early event in chemically induced skin tumors

BOLONTRADE MARCELA F, STERN MARIANA C, BINDER ROBERT L, GIMENEZ-CONTI IRMA B, CONTI CLAUDIO J

Austin, Texas, USA

Conferencia; 11th International Conference Carcinogenesis and Risk Assesment_ Environmental Skin Carcinogenesis: UV and Chemically Induced Cancer; 1997

In this study we have analyzed the vascular response induced in the two-stage carcinogenesis model in SENCAR mice. The role of angiogenesis has not been explored in this model, which is the paradigm of multistage carcinogenesis and a model for neoplastic lesions (e.g. colon carcinoma, bladder papilloma). We investigated if angiogenesis is involved in the formation of papillomas and in the progression from papilloma to carcinoma. To this end we analyzed the vasculature of normal and hyperplastic skin, focal epidermal hyperplasias that are precursors of papillomas, 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 malignant progression. We show here that angiogenesis is turned on in the earliest stages of papilloma formation. In the late stages, regardless of state of progression, the predominant response is an increase in the size of blood vessels. Thus, in the SENCAR mouse model, representative of exophytic tumors, the angiogenesis switch is a very early event, probably mechanistically related to the development of the primarily exophytic lesions. Therefore, the density of blood vessels can not be used as a predictor of malignant progression in this model.