Hepatocyte growth factor/scatter factor is an autocrine factor for human normal bronchial epithelial and lung carcinoma cells

Abstract

Hepatocyte growth factor (HGF) or scatter factor (SF) has been considered primarily as an endocrine/paracrine factor. We report here that HGF/SF mRNA was expressed by cultured human normal bronchial epithelial cells and many non-small cell lung carcinoma cell lines. Scatter activity was detected in the culture media of these cells, and this activity was inhibited by a neutralizing anti-recombinant human HGF antiserum. Immunostaining confirmed the presence of immunoreactive human HGF-like protein in the cytoplasm of these cultured cells, and in ciliated columnar epithelium of normal human bronchus/bronchioles. The met/HGF/SF receptor of these cultured cells was constitutively phosphorylated on tyrosine residues. A neutralizing anti-recombinant human HGF antiserum decreased the phosphorylation of the receptor, inhibited the proliferation of 45% of the non-small cell lung carcinoma cell lines studied, and stimulated the proliferation of normal bronchial epithelial cells. Altogether, the data demonstrate that HGF/SF and/or HGF-like protein is an autocrine factor for normal and neoplastic human bronchial epithelial cells in culture.