Expression of vascular endothelial growth factor (VEGF) and its receptors in human neuroblastoma

Angiogenic factors may play a role in the biology of neuroblastoma, a well vascularised tumour, which frequently spreads haematogenously. Therefore, w e analysed expression of vascular endothelial growth factor (VEGF) in six h uman neuroblastoma cell lines and five primary neuroblastomas. High VEGF le vels (1-3 ng/10(6) cells/day) were found in the supernatant of all cell lin es examined (SK-N-LO, SK-N-SH, LS, SH-SY5Y, IMR-32, Kelly). VEGF peptide wa s also detected in tissue homogenates from four of five primary tumours. Re verse transcript ion-polymerase chain reaction (RT-PCR) revealed that VEGF( 165) is the major isoform produced by neuroblastomas. In addition, all cell lines and primary tumours expressed the mitogenic VEGF receptor FLK-1, whi lst the non-mitogenic receptor FLT-1 was less frequently positive, suggesti ng that the tyrosine kinase FLK-1 is involved in malignant transformation o f neuroblastoma cells. However, neutralising antibodies to VEGF did not inh ibit growth of neuroblastoma cell lines, which argues against a role of VEG F as an autocrine growth factor, at least for cell lines in vitro. We concl ude that neuroblastoma cells produce VEGF, which may contribute to tumour v ascularisation, growth and invasion. (C) 1999 Elsevier Science Ltd. All rig hts reserved.