Expression of heparin-binding epidermal growth factor in human hepatocellular carcinoma

New therapies for hepatocellular carcinoma

“…The adult hepatocyte is the cell type in the organism where the EGFR is expressed at the highest levels, and it is thought to play a central role in liver regeneration after partial hepatectomy and tissue injury (Taub, 2004). Although this receptor is not commonly overexpressed in HCC cells, its continuous activation by ligands such as transforming growth factor-a (TGF-a), heparin-binding EGF (HB-EGF) or amphiregulin (AR), which are upregulated from the early stages of hepatocarcinogenesis, can be of significance for HCC development (Inui et al, 1994;Chung et al, 2000;Berasain et al, 2005a, b;Schiffer et al, 2005). These EGFR ligands are produced as transmembrane precursors, and need to be proteolitically released from the cell surface to signal in an autocrine or paracrine fashion (Yarden, 2001).…”

Dysregulation of growth factor signaling in human hepatocellular carcinoma

“…Heparin-binding EGF, which has been shown to be a more potent mitogen for hepatocytes than EGF, can be detected immunohistologically in 59-100% of HCCs, but not or only weakly in the surrounding parenchyma (Inui et al, 1994). Heparin-binding EGF expression appears to be a prognostic marker for disease-free survival and thus may be involved in early hepatocarcinogenesis (Ito et al, 2001a).…”

Membrane-anchored Heparin-binding Epidermal Growth Factor-like Growth Factor Acts as a Tumor Survival Factor in a Hepatoma Cell Line

“…in what is designated as a juxtacrine manner (7), and has been thought to contribute to cell growth like the soluble HB-EGF (sHB-EGF). High expression of HB-EGF was observed in human hepatocellular carcinoma tissues, but not in metastatic liver cancers or normal hepatocytes, suggesting that it is involved in the development or progression of hepatomas in an autocrine manner (8). During hepatocarcinogenesis in a rodent model, its expression was dramatically induced at the cancer (9).…”