EXPRESSION OF VASCULAR ENDOTHELIAL GROWTH-FACTOR (VEGF) IN RETINOBLASTOMA BUT NOT IN POSTERIOR UVEAL MELANOMA

All solid tumors must acquire a vascular stroma to grow beyond a minim al size. Vascular endothelial growth factor (VEGF) is a potent and spe cific angiogenic growth factor both in vitro and in vivo that may part icipate in the formation of the vascular tumor stroma. in the present study, we examined the expression of VEGF in the paraffin sections of 20 eyes harboring retinoblastoma or posterior uveal melanoma, but also in corresponding tumor cellines. By using in situ hybridization, we f ound that all but one of the retinoblastomas expressed VEGF mRNA. Part icularly high expression was detected in areas of loosely packed tumor cells with prominent chromatin. By contrast, none of the posterior uv eal melanomas expressed significant amounts of VEGF mRNA. Immunostaini ng with an antibody against VEGF confirmed that retinoblastomas, but n ot posterior uveal melanomas, also contained detectable VEGF protein. To further study the expression of VEGF in these tumor cells we perfor med Northern blotting on a retinoblastoma celline, Y79, and on an uvea l melanoma celline, OM431. Both of these cellines expressed low levels of VEGF mRNA under normal culture conditions. However, when the cells were cultured under hypoxic conditions, a strong increase in VEGF mRN A could be seen in Y79 cells but not in OM431 cells. By using a bioass ay, we also found that hypoxia stimulated the secretion of VEGF protei n into the culture medium of Y79 cells. In conclusion, we have shown t hat VEGF mRNA and protein are expressed in retinoblastomas but not in posterior uveal melanomas. Moreover we have shown that VEGF is hypoxia -inducible in retinoblastoma cells. These results suggest that focal h ypoxia may act as a stimulus for VEGF production in retinoblastomas, t hat in turn may contribute to tumor growth by stimulating the formatio n of a vascular stroma. (C) 1996 Academic Press Limited