Purification and partial characterization of hepatocyte growth factor from plasma of a patient with fulminant hepatic failure.

Abstract

Human hepatocyte growth factor (hHGF) has been purified 209,000-fold with 18% yield from plasma of a patient with fulminant hepatic failure. The purification involves heat treatment of.plasma, ammonium sulfate precipitation, and chromatography on Affi-Gel Blue, heparin-Sepharose, and hydroxylapatite. Purified hHGF shows several bands with molecular weights between 76,000 and 92,000. Each band shows growthstimulating activity on cultured hepatocytes which is proportional to the intensity of the band. After reduction of the sample with 2-mercaptoethanol, SDS-PAGE yields two chains with molecular weights of 31,500-34,500 and 54,000-65,000. The effect of hHGF on DNA synthesis by hepatocytes is halfmaximal at 3.5 ng/ml. hHGF stimulates proliferation of cultured hepatocytes more effectively than human epidermal growth factor (hEGF) or insulin, and the effect of hHGF is additive or synergistic with the maximal effects of hEGF and insulin. These results suggest that hHGF is a new growth factor which is different from hEGF.

HGF as a Circulating Biomarker of Onartuzumab Treatment in Patients with Advanced Solid Tumors

“…One possible explanation of the elevation in cHGF may be that onartuzumab displaces HGF binding to Met, resulting in increased circulating levels. HGF was discovered as a complex mitogen produced by liver kupfer cells and sinusoidal endothelial cells, capable of promoting liver regeneration via stimulation of hepatocytes (3,(30)(31)(32). cHGF is frequently associated with liver dysfunction or damage (31) and is elevated in liver diseases including cirrhosis and hepatitis independent of Met receptor expression (33).…”

Concomitant expression of hepatocyte growth factor (HGF), HGF activator and c‐met genes in human glioma cells in vitro

“…HGF is a multifunctional, heparin-binding glycoprotein initially identified as a potent mitogen for hepatocytes [1,2]. The c-met proto-oncogene product, a membrane-bound tyrosine kinase, was demonstrated to represent the high affinity HGF receptor suggesting the roles of HGF in tumor progression [6].…”

“…These processes are often mediated by polypeptide growth factors acting in either a paracrine or autocrine fashion. Hepatocyte growth factor (HGF) is a pleiotropic factor initially identified as a polypeptide growth factor for hepatocytes [1,2], and is indistinguishable from scatter factor (SF), a motility factor [3][4][5][6]. HGF functions as a mitogen for a variety of cell types, as a morphogen and as a motogen for some epithelial cells [6].…”

The five amino acid-deleted isoform of hepatocyte growth factor promotes carcinogenesis in transgenic mice

“…Hepatocyte growth factor (HGF) is a heparin binding glycoprotein originally puri®ed from serum and platelets based on its ability to induce a mitogenic response in normal hepatocytes in primary culture (Gohda et al, 1988;Nakamura et al, 1986;Zarnegar and Michalopoulos, 1989). Molecular cloning of the full length human, rat and mouse HGF-cDNAs has shown that the protein is encoded by a single open reading frame with highly conserved amino acids (Liu et al, 1994a;Miyazawa et al, 1991;Nakamura et al, 1989;Okajima et al, 1990).…”