Role of Angiogenic Growth Factors During Mouse Skin Tumor Development

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

Smithville, Texas, USA

Conferencia; Experimental Skin Carcinogenesis Conference; 1998

University of Texas MD Anderson Cancer Center_ Research Division

Angiogenesis is the sprouting of new blood vessels from pre-existing ones. Several growth factors have been implied in the regulation of angiogenesis; one of them is very specific for endothelial cells: VEGF (vascular endothelial growth factor). However, endothelial cells are also a target of several other growth factors, and its growth is regulated by these interactions at different points of their very tightly controlled cell cycle. Here we have analyzed the role of different isoforms of VEGF and Placenta Growth Fcator (PlGF) during the premalignant and malignant progression of mouse skin tumors. VEGF is comprised of 3 isoforms in the mouse which are product of alternative splicing of a single gene; some of these proteins are secreted. PlGF is also a secreted, dimeric, glycosilated protein capable of stimulating the growth of endothelial cells in vitro. It comproses at least 2 isoforms. Per se, this growth factor is not able to induce angiogenesis (at physiological concentrations) but can potentiate 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. Complexes between VEGF and PlGF were detected both in vivo and in vitro, suggesting that these interactions (probably involving primarily VEGF-1 and VEGF-2) could participate in the 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.