Differential Role of Angiogenic Growth Factors During Formation of Mouse Papillomas and Carcinomas

BOLONTRADE MARCELA F, RODRIGUEZ PUEBLA MARCELO, LACAVA MARGARET, LARCHER FERNANDO, JORCANO JOSE, CONTI CLAUDIO J

Philadelphia, PA, USA

Simposio; American Association for Cancer Research (AACR); 1999

Angiogenesis is the sprouting of new blood vessels from a pre-existing vascular network. This process is tightly controlled, being the result of the action of different growth factors on endothelial cells and other cells of the stroma. One of these factors, VEGF (vascular endothelial growth factor) is very specific for endothelial cells. VEGF comprises od 3 isoforms in mouse which are products of alternative splicing of a single gene and some of its proteins are secreted. Placenta Growth Factor (PlGF) is also a secreted, dimeric, glycosilated protein capable of stimulating the growth of endothelial cells in vitro.  It comprises at least 2 isoforms. Here we have analyzed the role of different isoforms of VEGF and PlGF during the premalignant and malignant progression of mouse skin tumors. Complexes between VEGF and PlGF were detected both in vivo and in vitro, suggesting that these heterodimers could participate in a dramatic increase in the density of blood vessels in early papillomas. According with this hypothesis, an increase in blood vessel density during papiloma formation was also detected in a previous work. We have also detected an isoform switching during progression to carcinogenesis, involving primarily the smaller isoform. Another growth factor involved in angiogenesis is bFGF (basic fibroblast growth factor) which is known as a potent angiogenic factor. We have detected an increase in he expression of bFGF during late stages of carcinogenesis, when the density of the blood vessels is stabilized, suggesting this growth factor may be more related with progression to carcinogenesis rather than with the histogenesis of the papillomas.