The Role of Endoglin in Hepatocellular Carcinoma

Int J Mol Sci. 2021 Mar 22;22(6):3208. doi: 10.3390/ijms22063208.

Abstract

Endoglin (CD105) is a type-1 integral transmembrane glycoprotein and coreceptor for transforming growth factor-β (TGF-β) ligands. The endoglin/TGF-β signaling pathway regulates hemostasis, cell proliferation/migration, extracellular matrix (ECM) synthesis and angiogenesis. Angiogenesis contributes to early progression, invasion, postoperative recurrence, and metastasis in hepatocellular carcinoma (HCC), one of the most widespread malignancies globally. Endoglin is overexpressed in newly formed HCC microvessels. It increases microvessel density in cirrhotic and regenerative HCC nodules. In addition, circulating endoglin is present in HCC patients, suggesting potential for use as a diagnostic or prognostic factor. HCC angiogenesis is dynamic and endoglin expression varies by stage. TRC105 (carotuximab) is an antibody against endoglin, and three of its clinical trials were related to liver diseases. A partial response was achieved when combining TRC105 with sorafenib. Although antiangiogenic therapy still carries some risks, combination therapy with endoglin inhibitors or other targeted therapies holds promise.

Keywords: angiogenesis; endoglin; hepatocellular carcinoma.

Publication types

  • Review

MeSH terms

  • Animals
  • Biomarkers, Tumor
  • Carcinoma, Hepatocellular / diagnosis
  • Carcinoma, Hepatocellular / etiology*
  • Carcinoma, Hepatocellular / metabolism*
  • Carcinoma, Hepatocellular / therapy
  • Disease Susceptibility*
  • Endoglin / blood
  • Endoglin / chemistry
  • Endoglin / genetics*
  • Endoglin / metabolism*
  • Endothelial Cells / metabolism
  • Gene Expression Regulation, Neoplastic
  • Hepacivirus / physiology
  • Hepatitis C / metabolism
  • Hepatitis C / virology
  • Humans
  • Liver Neoplasms / etiology*
  • Liver Neoplasms / metabolism*
  • Liver Neoplasms / pathology
  • Molecular Diagnostic Techniques
  • Molecular Targeted Therapy
  • Neovascularization, Pathologic / genetics
  • Neovascularization, Pathologic / metabolism
  • Signal Transduction
  • Structure-Activity Relationship
  • Viral Core Proteins / metabolism

Substances

  • Biomarkers, Tumor
  • Endoglin
  • Viral Core Proteins