title: C-terminal heptapeptide of gastrin inhibits astrocytomas motility by interacting with a new gastrin binding site.
abstract: It is well known that the amidated C-terminal part of gastrin is crucial for its interaction with the classical seven transmembrane domain receptors CCK-1 or CCK-2. Nevertheless, over the past 10 years, several groups have characterized new binding sites using peptides related to gastrin (particularly glycine-extended forms of gastrin) on various tumoral and nontumoral cell lines. In the present study, we focused on the human astrocytic tumoral cell line U373. Although it has been described that gastrin was able to inhibit the motility of these cells, we were unable to detect any classical CCK/gastrin receptor. On the other hand, by using the radiolabeled C-terminal heptapeptide of gastrin ((125)I-G-7), we evidenced a new binding site that possessed a pharmacological profile different from the classical CCK/gastrin receptors. This new gastrin binding site seemed to be coupled to G proteins and be implicated in c-Fos transcription gene. Moreover, we showed that G-7 was able to induce a strong inhibition of U373 cell migration, a crucial biological effect when we know that astrocytoma cells' migration in brain parenchyma constitutes a major feature of malignancy in astrocytic tumors.
authors.affiliation: Laboratory of Amino Acids, Peptides and Proteins, Free University of Brussels, Brussels, Belgium.
authors.forename: Julie
authors.initials: J
authors.lastname: Pannequin
authors.forename: Catherine
authors.initials: C
authors.lastname: Oiry
authors.forename: Caroline
authors.initials: C
authors.lastname: Morel
authors.forename: Jérôme
authors.initials: J
authors.lastname: Kucharczak
authors.forename: Isabelle
authors.initials: I
authors.lastname: Camby
authors.forename: Robert
authors.initials: R
authors.lastname: Kiss
authors.forename: Didier
authors.initials: D
authors.lastname: Gagne
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Galleyrand
authors.forename: Jean
authors.initials: J
authors.lastname: Martinez
mesh_terms: D000595:Amino Acid Sequence; D001254:Astrocytoma / Q000473:pathology*; D001665:Binding Sites; D001932:Brain Neoplasms / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism; D005755:Gastrins / Q000494:pharmacology*; D016762:Genes, fos / Q000235:genetics; D006801:Humans; D007295:Inositol Phosphates / Q000096:biosynthesis; D007457:Iodine Radioisotopes; D007553:Isotope Labeling; D007700:Kinetics; D008156:Luciferases / Q000378:metabolism; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000494:pharmacology*; D043886:Receptor, Cholecystokinin A; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin / Q000187:drug effects* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015290:Second Messenger Systems / Q000502:physiology; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D005755:Gastrins; D007295:Inositol Phosphates; D007457:Iodine Radioisotopes; D009842:Oligopeptides; D043886:Receptor, Cholecystokinin A; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin; D000242:Cyclic AMP; D008156:Luciferases