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Expression of vascular endothelial growth factor (VEGF) and VEGF receptors in human neuroblastomas
I Langer1, P Vertongen, J Perret
1Department of Pharmacology, Institute of Pharmacy, Université Libre de Bruxelles, Brussels, Belgium.
Background:
Vascular endothelial growth factor (VEGF) is a specific endothelial cell mitogen that stimulates angiogenesis and plays a crucial role in tumor growth. The aim of the present study was to evaluate the expression of VEGF and of its two high-affinity tyrosine kinase receptors (KDR and Flt-1) in neuroblastoma surgical samples and cell lines.
Procedure:
The VEGF, KDR, and Flt-1 mRNA expression in neuroblastoma surgical samples and cell lines was studied by RT-PCR. The receptors were identified in [(125)I]VEGF binding and in functional studies (effect on cell growth). VEGF production by neuroblastomas was investigated by the ELISA method.
Results:
It was possible 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. It was also possible to demonstrate that the SK-N-BE cell line expressed VEGF, KDR, and Flt-1 mRNAs as well as biologically active receptors: The cells bound [(125)I]-VEGF, and their growth was stimulated by exogenous VEGF. Moreover, VEGF protein could be detected in their culture conditioned medium.
Conclusions:
These results suggest that, in addition to its effect on angiogenesis, VEGF may affect neuroblastoma cell growth directly and could be an autocrine growth factor.