Vasoactive intestinal peptide (VIP) and VIP receptors: gene expression and growth modulation in medulloblastoma and other central primitive neuroectodermal tumors of childhood.
Vasoactive intestinal peptide (VIP) is a neuromodulator and growth regulator in the developing nervous system. We analyzed 10 primitive neuroectodermal tumor (PNET) cell lines, 29 central PNET (cPNET) and 17 tumors of the Ewing's sarcoma/peripheral PNET family (ESFT) using reverse transcriptase-polymerase chain reaction (RT-PCR) and Southern hybridization. Each of the 10 cell lines and 86.2% of cPNET expressed mRNA for VIP receptor 1 (VIPR1) compared to 52.9% of ESFT. VIPR2 was expressed in 75.8% of cPNET, in 28.6% of ESFT and in all 10 cell lines. cPNET demonstrated high-affinity binding of 125I-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.
Frühwald
M C
MC
Department of Pediatrics, Ohio State University, Columbus, USA.
O'Dorisio
M S
MS
Fleitz
J
J
Pietsch
T
T
Reubi
J C
JC
D001345:Autoradiography; D015139:Blotting, Southern; D002455:Cell Division / Q000502:physiology; D002648:Child; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006133:Growth Substances / Q000235:genetics*; D006801:Humans; D008297:Male; D008527:Medulloblastoma / Q000378:metabolism*; D018241:Neuroectodermal Tumors, Primitive, Peripheral / Q000378:metabolism*; D018005:Receptors, Vasoactive Intestinal Peptide / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D014660:Vasoactive Intestinal Peptide / Q000235:genetics*
D006133:Growth Substances; D018005:Receptors, Vasoactive Intestinal Peptide; D014660:Vasoactive Intestinal Peptide