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

BOLONTRADE, MARCELA F; BINDER, ROBERT L; GIMENEZ CONTI, IRMA B; CONTI, CLAUDIO J.

Orlando, Florida, USA

Conferencia; American Association for Cancer Research Special Conference “Angiogenesis and cancer”; 1998

American Association for Cancer Research

Angiogenesis is the sprouting of new blood vessels from a pre-existing vascular network. The endothelial cells that compose the tumor microvessels are target for several growth factors. Here we have analyzed the role of different isoforms of Vacsular Endothelial Growth Factor (VEGF) and Placenta Growth Factor (PlGF) during the premalignant and malignant progression of mouse skin tumors. VEGF is comprised of 3 isoforms in the mouse. PlGF is also a secreted, dimeric, glycosilated protein. It comprises at least 2 isoforms. PlGF is not able to induce angiogenesis in vivo but can potentate the action of VEGF; we have observed an isoform switching of VEGF-1 and VEGF-2, and an increase in the level of PlGF early in the formation of papillomas. We also analyzed the pattern of expression of basic Fibroblast Growth Factor (bFGF), a potent angiogenic factor. We detected an increase in the expression of bFGF during late stages of carcinogenesis. By analyzing the vasculature of normal and hyperplastic skin, focal epidermal hyperplasias that are precursors of papillomas, papillomas at different stages and squamous cell carcinomas, we demonstrated that angiogenesis is turned on in the earliest stages of papilloma formation. In 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, the angiogenesis switch is an very early event. VEGF and PlGF could participate in the dramatic increase in the density of blood vessels in early papillomas. bFGF could be related with progression to carcinogenesis rather than with the histogenesis of papillomas.