Hepatocyte growth factor is predominantly expressed by the carcinoma cells in non-small-cell lung cancer

Hepatocyte growth factor (HGF) exerts multifunctional regulatory roles in the growth, morphogenesis, differentiation, and motility of epithelial cells, and putatively plays important roles in tumor angiogenesis and metastasis. Aside from the full-length protein, 2 naturally occurring truncated HGF isoforms (NK1 and NK2) have been identified. Recent evidence suggests that a high level of HGF in surgically resected non-small-cell lung carcinoma (NSCLC) is a negative prognostic marker for NSCLC patients' survival. The origin of HGF in these tumors remains uncertain. We show here by in situ hybridization and immunohistochemistry that HGF messenger RNA (mRNA) and protein were predominantly expressed by the tumor cells in a high percentage of primary NSCLC. Stromal cell expression of HGF was limited to some lymphocytes and endothelial cells. Normal bronchial and bronchiolar epithelial cells also expressed HGF mRNA and immunoreactive protein. The mRNA transcripts and putative proteins of all 3 known HGF isoforms were detected in both normal lung and lung cancer tissues, but the full-length HGF was predominantly expressed. Our findings indicate that both autocrine and paracrine functions of HGF are likely to contribute to the pathobiology of lung cancer in vivo.