BOMBESIN STIMULATES THE IN-VITRO GROWTH OF A HUMAN GASTRIC-CANCER CELL-LINE

Bombesin (BBS) and its mammalian equivalent, gastrin-releasing peptide (GRP), exhibit diverse biological functions, including that of a neur otransmitter, a regulator of gastrointestinal hormone release, and a t rophic factor for various normal and neoplastic tissues. Bombesin stim ulates the growth of normal cells of the stomach, pancreas, and bronch ial epithelium as well as cells in breast cancer, gastrinoma, and smal l cell lung cancer. The purpose of this study was to determine whether BBS regulates the growth of a human gastric cancer cell line (SIIA) i n vitro, and if so, to examine the mechanisms of signal-transduction t hat are involved. We found that BBS stimulated the growth of SIIA cell s in vitro. The GRP receptor antagonists, BIM 26189 and BIM 26226, had no effect on growth of SIIA cells. Although these antagonists blocked the BBS-induced increase of [Ca2+](i), they failed to block the growt h-stimulatory effect of BBS. BBS stimulated intracellular tyrosine pho sphorylation of multipe proteins, with a predominant protein of appare nt molecular weight of 125 kDa. Inhibition of intracellular tyrosine k inases by tyrphostin blocked the growth-stimulatory effect of BBS on S IIA cells. These results indicate that BBS exerts its trophic effect o n SIIA cells through a receptor(s) linked to tyrosine kinase pathway, but not to the phospholipase C (PLC) pathway. (C) 1994 Wiley-Liss, Inc .