PARACRINE EFFECTS OF HEPATOCYTE GROWTH-FACTOR SCATTER FACTOR ON NON-SMALL-CELL LUNG-CARCINOMA CELL-LINES

We have studied the mitogenic, motogenic and morphogenic effects of he patocyte growth factor (HGF), also known as scatter factor (SF), on 15 non-small-cell lung carcinoma (NSCLC) cell lines that have had their ras genotype determined. HGF/SF stimulated proliferation in only three cell lines and exerted no mitogenic activity on six lines. The growth of the remaining six lines was inhibited, The mitogenic effects were not related to the ras genotype of these cell lines, but the inhibitor y effect was more commonly observed in cell lines with relatively high levels of Met/HGF receptor (HGFR) expression. HGF/SF induced or enhan ced both scatter activity on monolayer culture and single-cell invasio n in collagen gels in approximately half of these cell lines. Although the ras genotype of tumour cells did not influence the HGF/SF-induced motogenic activity, cell lines with the mutant ras genotype more comm only demonstrated a spontaneous motogenic activity than those with the wild-type ras genotype, When tumour cells were grown in collagen gels , HGF/SF induced irregular branching extensions of cell aggregates for med by five out of eight adenocarcinoma cell lines, but significant lu men morphogenesis was distinctly absent. The presence of autocrine HGF /SF loop in these tumour cell lines did not influence their spontaneou s or HGF/SF;induced mitogenic, motogenic or morphogenic activities. Ov erall, our data suggest that stimulation of cell motility, rather than proliferation or differentiation, is the predominant paracrine effect of HGF/SF on NSCLC cells in vitro.