HB-EGF is a paracrine growth stimulator for early tumor prestages in inflammation-associated hepatocarcinogenesis

Sagmeister, Sandra; Drucker, Claudia; Losert, Annemarie; Grusch, Michael; Daryabeigi, Anahita; Parzefall, Wolfram; Rohr-Udilova, Nataliya; Bichler, Christoph; Smedsrød, Bård; Kandioler, Daniela; Grünberger, Thomas; Wrba, Fritz; Schulte‐Hermann, Rolf; Grasl‐Kraupp, Bettina

doi:10.1016/j.jhep.2008.06.031

Cited by 24 publications

(29 citation statements)

References 41 publications

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“…These results, from experimental cell studies, mouse models, and clinical patient sections, strongly suggest that galectin-1 is an important effector factor that strengthens the feedback of lung cancer cells with the immune system. HB-EGF, a member of the EGF family, has been described as a mitogenic factor of various types of cells, including cancer cells (9,26). Overexpression of HB-EGF is correlated with tumor progression and poor patient survival in ovarian, colon, head and neck squamous cell carcinoma, stomach, and breast cancers (27,28).…”

Section: Discussionmentioning

confidence: 99%

“…Heparin-binding EGF-like growth factor (HB-EGF) is frequently produced as membrane-anchored precursor proteins that require cleavage by cell surface proteases, such as TNF␣-converting enzyme/a disintegrin and metalloproteinases 9 (TNF␣-converting enzyme/ADAM9) and 17 (TNF␣-converting enzyme/ADAM17), into soluble ligands (7)(8)(9)(10). Aberrant expression or ectodomain shedding of HB-EGF results in the development of various cancers: ovarian, pancreatic, liver, esophageal, melanoma, colon, gastric, and bladder, together with glioblastoma (9,11).…”

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confidence: 99%

“…Aberrant expression or ectodomain shedding of HB-EGF results in the development of various cancers: ovarian, pancreatic, liver, esophageal, melanoma, colon, gastric, and bladder, together with glioblastoma (9,11). HB-EGF has been demonstrated to promote cancer cell proliferation and migration by binding with EGF receptor (EGFR) or ERBB4 (12).…”

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confidence: 99%

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Lung Cancer-derived Galectin-1 Enhances Tumorigenic Potentiation of Tumor-associated Dendritic Cells by Expressing Heparin-binding EGF-like Growth Factor

Kuo

Huang

Cheng

et al. 2012

Journal of Biological Chemistry

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Background: Communication between cancer cells and immune cells in their microenvironment leads to cancer progression. Results: Lung cancer-derived galectin-1 stimulates HB-EGF expression and triggers a release mechanism in tumor-associated dendritic cells that stimulates tumor cell growth and invasion. Conclusion: The galectin-1/HB-EGF cycle between cancer and dendritic cells enhances lung cancer progression. Significance: Galectin-1 is a potential therapeutic target for inhibiting tumor-promoting immune cells in the tumor microenvironment.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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Lung Cancer-derived Galectin-1 Enhances Tumorigenic Potentiation of Tumor-associated Dendritic Cells by Expressing Heparin-binding EGF-like Growth Factor

Kuo

Huang

Cheng

et al. 2012

Journal of Biological Chemistry

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“…13). Increasing evidence has highlighted the importance of EGFR and its ligands EGF and TGF-a in hepatocarcinogenesis (14,15).…”

Section: Introductionmentioning

confidence: 99%

Vandetanib, an Inhibitor of VEGF Receptor-2 and EGF Receptor, Suppresses Tumor Development and Improves Prognosis of Liver Cancer in Mice

Inoue

Torimura

Nakamura

et al. 2012

Clinical Cancer Research

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Purpose: VEGF, EGF, and TGF-a are expressed in hepatocellular carcinomas (HCC) and play a role in its growth. Vandetanib, a multikinase inhibitor, suppresses the phosphorylation of VEGF receptor 2 (VEGFR-2) and EGF receptor (EGFR). The aim of this study was to clarify the antitumor effect of vandetanib in mouse HCCs.Experimental Design: We evaluated the effects of vandetanib on proliferation of human umbilical vein endothelial cells (HUVEC) and three hepatoma cell lines, as well as the phosphorylation of VEGFR-2 and EGFR in these cells. Mice were implanted with hepatoma cells subcutaneously or orthotopically in the liver and treated with 50 or 75 mg/kg vandetanib. We analyzed the effects of treatment on tumor cell proliferation and apoptosis, vessel density, phosphorylation of VEGFR-2 and EGFR, and production of VEGF, TGF-a, and EGF in tumor tissues. Adverse events on vandetanib administration were also investigated.Results: Vandetanib suppressed phosphorylation of VEGFR-2 in HUVECs and EGFR in hepatoma cells and inhibited cell proliferation. In tumor-bearing mice, vandetanib suppressed phosphorylation of VEGFR-2 and EGFR in tumor tissues, significantly reduced tumor vessel density, enhanced tumor cell apoptosis, suppressed tumor growth, improved survival, reduced number of intrahepatic metastases, and upregulated VEGF, TGF-a, and EGF in tumor tissues. Treatment with vandetanib was not associated with serious adverse events, including alanine aminotransferase abnormality, bone marrow suppression, or body weight loss.Conclusions: The antitumor effects of vandetanib in mice suggest that it is a potentially suitable and safe chemotherapeutic agent for HCCs.

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“…Thus, the absence of Ecadherin in biliary epithelial cells should activate the EGFR pathway leading to TGF-␤1 production. TGF-␤1 will increase HB-EGF production by mesenchymal cells of the portal space that will in turn favor biliary epithelial cell proliferation and EMT through EGFR signaling [22][23][24]. Interestingly, the observation of CCC tumors in mice lacking hepatic Ecadherin recapitulates the pathophysiological continuum of PSC, a well-known pathology associated with CCC development [25].…”

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confidence: 99%

E-cadherin, guardian of liver physiology

Gonzalez-Sanchez

Vaquero

Fouassier

et al. 2015

Clinics and Research in Hepatology and Gastroenterology

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E-cadherin is a cell-to-cell adhesion molecule involved in epithelial cell behavior, tissue formation and cancer suppression. In the liver, E-cadherin is expressed by hepatocytes and biliary epithelial cells. However, the exact role of E-cadherin in hepatic pathophysiology remains largely unknown. Recently, specific loss of E-cadherin in liver epithelial cells has been shown to favor periportal fibrosis, periportal inflammation and liver cancer progression, suggesting that E-cadherin is a central liver protector.

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HB-EGF is a paracrine growth stimulator for early tumor prestages in inflammation-associated hepatocarcinogenesis

Cited by 24 publications

References 41 publications

Lung Cancer-derived Galectin-1 Enhances Tumorigenic Potentiation of Tumor-associated Dendritic Cells by Expressing Heparin-binding EGF-like Growth Factor

Lung Cancer-derived Galectin-1 Enhances Tumorigenic Potentiation of Tumor-associated Dendritic Cells by Expressing Heparin-binding EGF-like Growth Factor

Vandetanib, an Inhibitor of VEGF Receptor-2 and EGF Receptor, Suppresses Tumor Development and Improves Prognosis of Liver Cancer in Mice

E-cadherin, guardian of liver physiology

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