Colorectal cancers express significant amounts of immature glycine-extended gastrin (G-Gly) and G-Gly is able to stimulate cell proliferation in colonic cell lines and mucosa. Here we wished to investigate whether G17-Gly promote the invasiveness of LoVo human colonic cancer cells, a process which requires degradation of extracellular matrix by proteases and concomitant induction of cell migration. We confirmed that LoVo cells express gastrin and gastrin/CCK-B receptor mRNAs. We showed that these cells secrete matrix metalloproteinase (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 artificial 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 and suggest a novel potential role for this peptide in the metastatic process of colonic cancers in vivo.
Copyright 2001 Academic Press.