Angiogenesis is an early event in the development of chemically induced skin tumors

In this study we have analyzed the vascular response induced in the two-sta ge carcinogenesis model in SENCAR mice. The role of angiogenesis has not be en explored in this model, which is the paradigm of multistage carcinogenes is and a model for neoplastic lesions derived from exophytic premalignant l esions (e.g, colon carcinoma, bladder papilloma). We investigated if angiog enesis is involved in the formation of papillomas and in the progression fr om papilloma to carcinoma. To this end we analyzed the vasculature of norma l and hyperplastic skin, focal epidermal hyperplasias that are precursors o f papillomas, papillomas at different stages and squamous cell carcinomas. We also analyzed the vascularization of papillomas induced in two strains o f mice that differ in their susceptibility to malignant progression. We sho w here that angiogenesis is turned on in the earliest stages of papilloma f ormation. In late stages, regardless of state of progression, the predomina nt response is an increase in the size of blood vessels. Thus, in the SENCA R 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 cannot be used as a predictor of malignant progression in this model.