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 endo thelial cells in vitro, promotes neoangiogenesis in vivo and increases the permeability of the vascular endothelium. VEGF overexpression occ urs in several cultured tumor cell lines and in certain human malignan cies, Placenta growth factor (PIGF) is a recently identified growth fa ctor for endothelial cells (EC); PIGF strongly potentiates both the pr oliferative and the permeabilization effects exerted by VEGF on the va scular endothelium, To uncover the molecular mechanisms underlying neo angiogenesis in human thyroid tumors, we have analysed VEGF and PIGF e xpression in a panel of thyroid carcinoma cell lines with different tu morigenic potential as well as in human primary thyroid tumors, We sho w that a high tumorigenic potential is associated with an elevated VEG F expression in human thyroid tumor cell lines, Furthermore, VEGF over expression occurs in 5/5 highly malignant anaplastic carcinomas, Papil lary and follicular carcinomas express intermediate levels of VEGF mRN A. In contrast, PIGF expression is severely down regulated in the majo rity of thyroid tumor cell lines and in tumors, Furthermore, we show t hat both the VEGF receptors, FLT-1 and flk/KDR, are expressed in endot helial cells that line tumor-embedded microvascular vessels, suggestin g that VEGF but not PIGF, contributes to thyroid tumor development.