Expression of vascular endothelial growth factor (VEGF) and VEGF receptorsin human neuroblastomas

Background. Vascular endothelial growth factor (VEGF) is a specific endothe lial cell mitogen that stimulates angiogenesis and plays a crucial role in tumor growth. The aim of the present study was to evaluate the expression o f VEGF and of its two high-affinity tyrosine kinase receptors (KDR and Flt- 1) in neuroblastoma surgical samples and cell lines. Procedure. The VEGF, K DR, and Flt-1 mRNA expression in neuroblastoma surgical samples and cell li nes was studied by RT-PCR. The receptors were identified in [I-125]VEGF bin ding and in functional studies (effect on cell growth). VEGF production by neuroblastomas was investigated by the ELISA method. Results. It was possib le to observe the mRNAs encoding for VEGF and its two receptors in some of the surgical specimens examined, including most of the high-grade tumors, i t was also possible to demonstrate that the SK-N-BE cell line expressed VEG F, KDR, and Flt-1 mRNAs as well as biologically active receptors: The cells bound [I-125]-VEGF, and their growth was stimulated by exogenous VEGF. Mor eover, VEGF protein could be detected in their culture conditioned medium. Conclusions. These results suggest that, in addition to its effect on angio genesis, VEGF may affect neuroblastoma cell growth directly and could he an autocrine growth factor. (C) 2000 Wiley-Liss, Inc.