VASCULAR ENDOTHELIAL GROWTH-FACTOR CONFERS A GROWTH ADVANTAGE IN-VITRO AND IN-VIVO TO STROMAL CELLS CULTURED FROM NEONATAL HEMANGIOMAS

Neonatal hemangioma is a common benign proliferation of unorganized st ructures containing stromal and capillary endothelial cells. We tested the hypothesis that such cell proliferation might result from the rel ease by stromal cells of endothelial cell mitogens. Stromal cells cult ured from biopsies of surgically removed life-threatening hemangiomas released an endothelial cell mitogen in vitro that was indistinguishab le from vascular endothelial growth factor (VEGF) based on independent criteria such as affinity chromatography for heparin or anti-VEGF IgG and radioreceptor assay, A functional product of the KDR gene encodin g a cogitate VEGF receptor was also expressed by these stromal cells. Transient transfection with antisense oligonucleotides targeted on the translation initiation codon of KDR abolished its tyrosine phosphoryl ation and mitogenic response of neonatal hemangioma cells to VEGF, con firming the existence of art autocrine loop of proliferation. When gra fted in nude mice, these stromal cells elicited an angiogenic response that was blocked by neutralizing anti-VEGF IgG. These results might p rovide a clue to the importance of stromal cells in the pathogeny of n eonatal hemangiomas.