Angiogenesis is an early event related with the histogenesis of papillomas in chemically induced skin tumors.

BOLONTRADE, MARCELA F.; LARCHER, FERNANDO; JORCANO, JOSÉ; GIMENEZ CONTI, IRMA B.; ROLIG, RHONDA; CONTI, CLAUDIO J.

New Orleans, Louisiana.

Simposio; 89no Encuentro Anual. American Association for Cancer Research (AACR).; 1998

American Association for Cancer Research (AACR).

We analyzed the role of angiogenesis during the development of papillomas and carcinomas induced by a chemical carcinogenesis protocol in SENCAR mice. We have previously determined the density and distribution of blood vessels in normal and hyperplastic skin as well as in papillomas and carcinomas. Blood vessel density reach the maximum levels at early stages of papilloma development and appear not to increase as tumor progress to squamous cell carcinomas. However, marked changes in the size of blood vessels were seen in the more advanced papillomas and carcinomas. Thus, angiogenesis seems to play a role in the histogenesis of papillomas and the angiogenic switch appears to be an early event in the mouse skin carcinogenesis model. In order to study the mechanisms involved in the angiogenesis switch and in the changes in blood vessel morphology during progression we analyzed in more detail the expression of VEGF (vascular endothelial growth factor), which was previously shown to be expressed in the mouse skin tumors. Now, we show changes in the relative expression of the different isoforms of VEGF during papilloma progression with predominance of the lower molecular weight forms in advanced papillomas. The appearance of these isoforms coincides with the morphological changes in blood vessels. This suggests that the different isforms of VEGF would be playing a distinct role during papilloma formation. We also have analyzed FGF-2, another mitogen for endothelial cells, which was shown also to be expressed in papillomas and carcinomas in this model. Taken together these results suggest that the angiogenesis changes observed in the mouse skin model can be attributed to the interaction of different angiogenesis factors.