UP-REGULATION OF VASCULAR ENDOTHELIAL GROWTH-FACTOR (VEGF) AND DOWN-REGULATION OF PLACENTA GROWTH-FACTOR (PIGF) ASSOCIATED WITH MALIGNANCY IN HUMAN THYROID-TUMORS AND CELL-LINES

Vascular endothelial growth factor (VEGF) is a potent mitogen for endothelial cells in vitro, promotes neoangiogenesis in vivo and increases the permeability of the vascular endothelium. VEGF overexpression occurs in several cultured tumor cell lines and in certain human malignancies, Placenta growth factor (PIGF) is a recently identified growth factor for endothelial cells (EC); PIGF strongly potentiates both the proliferative and the permeabilization effects exerted by VEGF on the vascular endothelium, To uncover the molecular mechanisms underlying neoangiogenesis in human thyroid tumors, we have analysed VEGF and PIGF expression in a panel of thyroid carcinoma cell lines with different tumorigenic potential as well as in human primary thyroid tumors, We show that a high tumorigenic potential is associated with an elevated VEGF expression in human thyroid tumor cell lines, Furthermore, VEGF overexpression occurs in 5/5 highly malignant anaplastic carcinomas, Papillary and follicular carcinomas express intermediate levels of VEGF mRNA. In contrast, PIGF expression is severely down regulated in the majority of thyroid tumor cell lines and in tumors, Furthermore, we show that both the VEGF receptors, FLT-1 and flk/KDR, are expressed in endothelial cells that line tumor-embedded microvascular vessels, suggesting that VEGF but not PIGF, contributes to thyroid tumor development.