Overexpression and activation of hepatocyte growth factor scatter factor in human non-small-cell lung carcinomas

• Type of Material: Article
• Authors: M Olivero, Institute for Cancer Research and Treatment IRCC; Monica Rizzo, Emory University; R Madeddu, University of Sassari; C Casadio, University of Torino; S Pennacchietti, Institute for Cancer Research and Treatment IRCC; MR Nicotra, Regina Elena Cancer Research Institute; M Prat, Institute for Cancer Research and Treatment IRCC; G Maggi, University of Torino; N Arena, University of Sassari; PG Natali, Regina Elena Cancer Research Institute; PM Comoglio, Institute for Cancer Research and Treatment IRCC; MF DiRenzo, University of Sassari
• Language: English
• Date: 1996-12-01
• Publisher: Cancer Research UK
• Publication Version: Final Published Version
• Copyright Statement: © 1996 Stockton Press.
• License: Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1038/bjc.1996.646
• Title of Journal or Parent Work: British Journal of Cancer
• ISSN: 0007-0920
• Volume: 74
• Issue: 12
• Start Page: 1862
• End Page: 1868
• Grant/Funding Information: This work was supported by grants from the Associazione Italiana Ricerche sul Cancro (AIRC) to PMC, PGN and MFD and from the Italian Consiglio Nazionale delle Ricerche (CNR, special project ACRO; to MFD, PMC, MP and PGN). MO is supported by an AIRC fellowship.
• Keywords: EPITHELIAL-CELLS; MESSENGER-RNA; TYROSINE KINASE; PLASMINOGEN ACTIVATORS; SINGLE-CHAIN; MET HGF RECEPTOR; PROTEOLYTIC ACTIVATION; SERINE-PROTEASE; Met receptor; human cancer; MOLECULAR-CLONING; Oncology; FACTOR GENE; Life Sciences & Biomedicine; hepatocyte growth factor scatter factor; non-small-cell lung cancer
• Research Categories: Health Sciences, Pathology; Health Sciences, Oncology

Abstract

Hepatocyte growth factor/scatter factor (HGF/SF) stimulates the invasive growth of epithelial cells via the c-MET oncogene-encoded receptor. In normal lung, both the receptor and the ligand are detected, and the latter is known to be a mitogenic and a motogenic factor for both cultured bronchial epithelial cells and non-small-cell carcinoma lines. Here, ligand and receptor expression was examined in 42 samples of primary human non-small-cell lung carcinoma of different histotype. Each carcinoma sample was compared with adjacent normal lung tissue. The Met/HGF receptor was found to be 2 to 10-fold increased in 25% of carcinoma samples (P = 0.0113). The ligand, HGF/SF, was found to be 10 to 100-fold overexpressed in carcinoma samples (P < 0.0001). Notably, while HGF/SF was occasionally detectable and found exclusively as a single-chain inactive precursor in normal tissues, it was constantly in the biologically-active heterodimeric form in carcinomas. Immunohistochemical staining showed homogeneous expression of both the receptor and the ligand in carcinoma samples, whereas staining was barely delectable in their normal counterparts. These data show that HGF/SF is overexpressed and consistently activated in non-small-cell lung carcinomas and may contribute to the invasive growth of lung cancer.