Stimulation of gastrin-CCK_B receptor promotes migration of gastric AGS cells via multiple paracrine pathways

Abstract

Responses to G protein-coupled receptor stimulation may be mediated by paracrine factors. We have developed a coculture system to study paracrine regulation of migration of gastric epithelial (AGS) cells after stimulation of gastrin-CCK(B) receptors. In cells expressing this receptor, G-17 stimulated migration by activation of protein kinase C. However, G-17 also stimulated the migration of cells expressing green fluorescent protein, but not the receptor, when they were cocultured with receptor-expressing cells consistent with activation of paracrine signals. The use of various pharmacological inhibitors indicated that gastrin stimulated migration via activation of the EGF receptor (EGR-R), the erbB-2 receptor tyrosine kinase, and the MAP kinase pathway. However, gastrin also released fibroblast growth factor (FGF)-1, and migration was inhibited by the FGF receptor tyrosine kinase inhibitor SU-5402. Flow cytometry indicated that in both cell types, gastrin increased MAP kinase via activation of EGF-R but not FGF-R1 or erbB-2. We conclude that gastrin-CCK(B) receptors stimulate epithelial cell migration partly via paracrine mechanisms; transactivation of EGF-R is only one component of the paracrine pathway.

Helicobacter pyloriInduces Plasminogen Activator Inhibitor 2 in Gastric Epithelial Cells through Nuclear Factor-κB and RhoA

“…10A). Similarly, in a system in which receptor (AGS-G R cells) and reporter cells (AGS-GFP cells) were cocultured and exposed to gastrin (8), there was nuclear translocation of p65-dsRed in the former but not the latter in response to gastrin (1-10 nM; Fig. 8, D-I; Fig.…”

“…After an additional 18 h, the cells were transferred to the motorized stage of an inverted epifluorescence microscope (DMIRE; Leica; Ref. 8,22). Samples, stage, and optics were enclosed in a heated chamber (Solent Scientific, Portsmouth, United Kingdom) and gassed with 5%CO 2 / 95% O 2 .…”

Gastrin-mediated activation of cyclin D1 transcription involves β-catenin and CREB pathways in gastric cancer cells

“…The fact that G-17 can induce cyclin D1 expression (Zhukova et al, 2001;Song et al, 2003) indirectly reveals its growth-promoting/ oncogenic function, since cyclin D1 functions as an oncogene in several kinds of tumor tissues (Motokura and Arnold, 1993), and new evidence suggests a role in invasion as well (Arato-Ohshima and Sawa, 1999;Jung et al, 2001). The CCK2 receptor (Watson et al, 2000) and gastrin (Bierkamp et al, 2002;Noble et al, 2003) have been implicated in regulating the invasion pathway as well. The elucidation of the pathway by which G-17 4), KCREB (lanes 7 and 8) or both (lanes 11 and 12) and treated as in (a).…”

Constitutively active CCK2 receptor splice variant increases Src-dependent HIF-1α expression and tumor growth

“…The peptide hormone gastrin and its biosynthetic precursors stimulate gastrointestinal (GI) cancer cell growth, migration (Noble et al, 2003) and invasion (Wroblewski et al, 2002). The actions of gastrin are mediated by the cholecystokinin-2 (CCK 2 )/gastrin receptor, a member of the G protein-coupled receptor superfamily.…”