Paracrine effects of hepatocyte growth factor/scatter factor on non-small-cell lung carcinoma cell lines

• Published in: British journal of cancer Vol. 77; no. 12; pp. 2162 - 2170
• Main Authors: YI, S, CHEN, J.-R, VIALLET, J, SCHWALL, R. H, NAKAMURA, T, TSAO, M.-S
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 01.06.1998
• Subjects: Biological and medical sciences; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - pathology; Cell Division - drug effects; Genes, ras; Genotype; Hepatocyte Growth Factor - pharmacology; Humans; Lung Neoplasms - genetics; Lung Neoplasms - pathology; Medical sciences; Mitogens - pharmacology; Neoplasm Invasiveness; Phenotype; Pneumology; Recombinant Proteins - pharmacology; Stimulation, Chemical; Tumor Cells, Cultured - drug effects; Tumors of the respiratory system and mediastinum; Human; Lung disease; Respiratory disease; Hepatocyte growth factor; Mitosis; Malignant tumor; Cell differentiation; Experimental study; In vitro; Bronchopulmonary; Autocrine secretion; Morphological analysis; Bronchus disease; Biological effect; Non small cell carcinoma
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/bjc.1998.361

We have studied the mitogenic, motogenic and morphogenic effects of hepatocyte 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 inhibitory effect was more commonly observed in cell lines with relatively high levels of Met/HGF receptor (HGFR) expression. HGF/SF induced or enhanced both scatter activity on monolayer culture and single-cell invasion 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 commonly 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 formed by five out of eight adenocarcinoma cell lines, but significant lumen morphogenesis was distinctly absent. The presence of autocrine HGF/SF loop in these tumour cell lines did not influence their spontaneous or HGF/SF-induced mitogenic, motogenic or morphogenic activities. Overall, 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.