C-terminal heptapeptide of gastrin inhibits astrocytomas motility by interacting with a new gastrin binding site.
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.
Pannequin
Julie
J
Laboratory of Amino Acids, Peptides and Proteins, Free University of Brussels, Brussels, Belgium.
Oiry
Catherine
C
Morel
Caroline
C
Kucharczak
Jérôme
J
Camby
Isabelle
I
Kiss
Robert
R
Gagne
Didier
D
Galleyrand
Jean-Claude
JC
Martinez
Jean
J
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
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