Vasoactive intestinal peptide (VIP) and VIP receptors: Gene expression andgrowth modulation in medulloblastoma and other central primitive neuroectodermal tumors of childhood

Vasoactive intestinal peptide (VIP) is a neuromodulator and growth regulato r in the developing nervous system. We analyzed 10 primitive neuroectoderma l tumor (PNET) cell lines, 29 central PNET (cPNET) and 17 tumors of the Ewi ng's sarcoma/peripheral PNET family (ESFT) using reverse transcriptase-poly merase chain reaction (RT-PCR) and Southern hybridization, Each of the 10 c ell lines and 86.2% of cPNET expressed mRNA for VIP receptor I (VIPR1) comp ared to 52.9% of ESFT. VIPR2 was expressed in 75.8% of cPNET, in 28.6% of E SFT and in all 10 cell lines. cPNET demonstrated high-affinity binding of I -125-VIP on quantitative autoradiography and in competitive binding assays. VIP inhibited tumor cell proliferation in a dose-dependent manner in 5 of 7 PNET cell lines. We conclude that VIPR1 and VIPR2 are highly expressed in cPNET and demonstrate that VIP is a growth modulator in these tumors. Int. J. Cancer 81:165-173, 1999. (C) 1999 Wiley-Liss, Inc.