Glycine-extended gastrin promotes the invasiveness of human colon cancer cells

Colorectal cancers express significant amounts of immature glycine-extended gastrin (G-Cly) and G-GIST is able to stimulate cell proliferation in colo nic cell lines and mucose. Here we wished to investigate whether G17-Gly pr omote the invasiveness of LoVo human colonic cancer cells, a process which requires degradation of extracellular matrix by proteases and concomitant i nduction of cell migration. We confirmed that LoVo cells express gastrin an d gastrin/CCK-B receptor mRNAs, We showed that these cells secrete matrix m etalloproteinase (MMP)-1, -2, and -9. The function of MMP being to degrade components of extracellular matrix, they may thus favor cell migration. As compared to controls, G17-Gly (10(-7) to 10(-12) M) significantly enhanced about two to three times the LoVo cell migration through Matrigel, an artif icial basement matrix barrier. Moreover, G17-Gly increased and gastrin/CCK- B receptor antagonists decreased MMP secretion in conditioned culture media of LoVo cells. Our findings show that physiological doses of incompletely processed form of gastrin induce the invasiveness of tumor cells in vitro a nd suggest a novel potential role for this peptide in the metastatic proces s of colonic cancers in vivo. (C) 2001 Academic Press.