Vol. 302, Issue 1, 274-282, July 2002

C-Terminal Heptapeptide of Gastrin Inhibits Astrocytomas Motility by Interacting with a New Gastrin Binding Site

Julie Pannequin, Catherine Oiry, Caroline Morel, Jérôme Kucharczak, Isabelle Camby, Robert Kiss, Didier Gagne, Jean-Claude Galleyrand and Jean Martinez

Laboratoire des Amino Acides, Peptides et Protéines (J.P., C.O., C.M., J.K., D.G., J.-C.G., J.M.); and Laboratoire d'Histopathologie, Faculté de Médecine, Université Libre de Bruxelles, Brussels, Belgium (I.C., R.K.)

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 (¹²⁵I-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.