Selective upregulation of vascular endothelial growth factor receptors neuropilin-1 and -2 in human neuroblastoma.

Abstract

Recent studies show that vascular endothelial growth factor (VEGF) and its receptors Flt-1 and KDR, and a series of other angiogenic molecules, are upregulated in advanced but not low stage human neuroblastoma. Neuropilin-1 and 2 (NRP) are novel specific receptors of VEGF(165), whose role is unknown in human neuroblastoma. Tissue biopsies of 37 children with Stage I-IV neuroblastoma were obtained, as well as biopsies of 7 normal adrenals as controls. The mRNA expression of VEGF(165) and its receptors Flt-1, KDR, NRP1, and NRP2 was evaluated by real-time reverse transcription polymerase chain reaction. NRP protein expression was detected by immunocytochemistry and Western blotting. VEGF(165) mRNA was upregulated in Stage III and IV and Flt-1 and KDR gene expression was increased in Stage III, while NRP1 and 2 mRNA and protein levels were higher in Stages I-IV vs. controls (P < 0.05). NRP was expressed in vascular endothelial but not tumor cells. These results show for the first time that human neuroblastoma expresses NRP, and that NRP co-regulates VEGF angiogenic effect in human neuroblastoma. NRP might be a sensitive angiogenic measure of VEGF systems in neuroblastoma, particularly in its early stages.