Effects of the vasoactive intestinal peptide (VIP) and related peptides on glioblastoma cell growth in vitro.
The growth rate of numerous cancer cell lines is regulated in part by actions of neuropeptides of the vasoactive intestinal peptide (VIP) family, which also includes pituitary adenylate cyclase-activating peptide (PACAP), glucagon, and peptide histidine/isoleucine (PHI). The aim of this work was to investigate the effect of these peptides on the growth of the rat glioblastoma cell line C6 in vitro. We also sought to determine which binding sites were correlated with the effects observed. Proliferation studies performed by means of a CyQuant trade mark assay showed that VIP and PACAP strongly stimulated C6 cell proliferation at most of the concentrations tested, whereas PHI increased cell proliferation only when associated with VIP. Two growth hormone-releasing factor (GRF) derivatives and the VIP antagonist hybrid peptide neurotensin-VIP were able to inhibit VIP-induced cell growth stimulation, even at very low concentrations. Binding experiments carried out on intact cultured C6 cells, using 125I-labeled VIP and PACAP as tracers, revealed that the effects of the peptides on cell growth were correlated with the expression on C6 cells of polyvalent high-affinity VIP-PACAP binding sites and of a second subtype corresponding to very high-affinity VIP-selective binding species. The latter subtype, which interacted poorly with PACAP with a 10,000-fold lower affinity than VIP, might mediate the antagonist effects of neurotensin- VIP and of both GRF derivatives on VIP-induced cell growth stimulation.
Laboratoire de Biologie des Interactions Cellulaires, CNRS UMR 6558, Faculté de Sciences, Université de Poitiers, 86022 Poitiers, France.
Christine
C
Dufes
Céline
C
Alleaume
Alicia
A
Montoni
Jean-Christophe
JC
Olivier
Jean-Marc
JM
Muller
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001665:Binding Sites / Q000187:drug effects / Q000502:physiology; D001667:Binding, Competitive / Q000187:drug effects / Q000502:physiology; D001932:Brain Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology*; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced / Q000187:drug effects / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005909:Glioblastoma / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D013007:Growth Hormone-Releasing Hormone / Q000494:pharmacology; D009479:Neuropeptides / Q000494:pharmacology; D009496:Neurotensin / Q000494:pharmacology; D010451:Peptide PHI / Q000494:pharmacology; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D051381:Rats; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism; D014660:Vasoactive Intestinal Peptide / Q000037:antagonists & inhibitors*
C495403:Adcyap1 protein, rat; D000970:Antineoplastic Agents; D009479:Neuropeptides; D010451:Peptide PHI; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D011956:Receptors, Cell Surface; D014660:Vasoactive Intestinal Peptide; D009496:Neurotensin; D013007:Growth Hormone-Releasing Hormone