INTERLEUKIN-4 INHIBITS HEPATOCYTE GROWTH FACTOR-INDUCED INVASION AND MIGRATION OF COLON CARCINOMAS

Hepatocyte growth factor (HGF) is known to have a number of biological properties including promoting tumor progression of human carcinomas. Metastasis involves a number of events that are attributed to inducti on by paracrine factors such as HGF. Identification of natural inhibit ors of these events would allow better control of tumor progression. R ecently we demonstrated that interleukin 4 (IL-4) can regulate prolife ration of various human carcinoma cell lines. In the present study, we used established human colon carcinoma cell lines and primary colon c arcinoma cell cultures to determine if IL-4 could regulate HGF-induced cell proliferation and other events of tumor progression such as MMP (matrix metalloproteinases)-1, -2, and -9 production, cell migration a nd cell-matrix invasive activity. All colon carcinoma cell lines expre ssed HGF and IL-4 receptors. IL-4 significantly inhibited HGF-induced proliferation of one cell line. Cell-matrix invasion was significantly enhanced by HGF (0.1-10 ng/ml); IL-4 (1-10 U/ml) significantly inhibi ted HGF-induced invasion in a dose-dependent manner. IL-4 also inhibit ed HGF-induced cell-matrix invasion of metastatic colon carcinoma cell s and HGF-induced cell migration. HGF enhanced MMP-1, -2, and -9 produ ction by cell lines. This effect could be inhibited by IL-4. These fin dings indicate that IL-4 is a potent inhibitor of HGF-induced invasion and metastasis-related functions of human colon carcinoma cells. (C) 1996 Wiley-Liss, Inc.