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Role of Endoglin (CD105) in the Progression of Hepatocellular Carcinoma and Anti-Angiogenic Therapy

The liver is perfused by both arterial and venous blood, with a resulting abnormal microenvironment selecting for more-aggressive malignancies. Hepatocellular carcinoma (HCC) is the most frequent primary liver cancer, the sixth most common cancer globally, and the third leading cause of cancer-relat...

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Autores principales: Kasprzak, Aldona, Adamek, Agnieszka
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6321450/
https://www.ncbi.nlm.nih.gov/pubmed/30563158
http://dx.doi.org/10.3390/ijms19123887
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author Kasprzak, Aldona
Adamek, Agnieszka
author_facet Kasprzak, Aldona
Adamek, Agnieszka
author_sort Kasprzak, Aldona
collection PubMed
description The liver is perfused by both arterial and venous blood, with a resulting abnormal microenvironment selecting for more-aggressive malignancies. Hepatocellular carcinoma (HCC) is the most frequent primary liver cancer, the sixth most common cancer globally, and the third leading cause of cancer-related mortality worldwide. HCC is characterized by its hypervascularization. Improving the efficiency of anti-angiogenic treatment and mitigation of anti-angiogenic drug resistance are the top priorities in the development of non-surgical HCC therapies. Endoglin (CD105), a transmembrane glycoprotein, is one of the transforming growth factor β (TGF-β) co-receptors. Involvement of that protein in angiogenesis of solid tumours is well documented. Endoglin is a marker of activated endothelial cells (ECs), and is preferentially expressed in the angiogenic endothelium of solid tumours, including HCC. HCC is associated with changes in CD105-positive ECs within and around the tumour. The large spectrum of endoglin effects in the liver is cell-type- and HCC- stage-specific. High expression of endoglin in non-tumour tissue suggests that this microenvironment might play an especially important role in the progression of HCC. Evaluation of tissue expression, as well as serum concentrations of this glycoprotein in HCC, tends to confirm its role as an important biomarker in HCC diagnosis and prognosis. The role of endoglin in liver fibrosis and HCC progression also makes it an attractive therapeutic target. Despite these facts, the exact molecular mechanisms of endoglin functioning in hepatocarcinogenesis are still poorly understood. This review summarizes the current data concerning the role and signalling pathways of endoglin in hepatocellular carcinoma development and progression, and provides an overview of the strategies available for a specific targeting of CD105 in anti-angiogenic therapy in HCC.
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spelling pubmed-63214502019-01-07 Role of Endoglin (CD105) in the Progression of Hepatocellular Carcinoma and Anti-Angiogenic Therapy Kasprzak, Aldona Adamek, Agnieszka Int J Mol Sci Review The liver is perfused by both arterial and venous blood, with a resulting abnormal microenvironment selecting for more-aggressive malignancies. Hepatocellular carcinoma (HCC) is the most frequent primary liver cancer, the sixth most common cancer globally, and the third leading cause of cancer-related mortality worldwide. HCC is characterized by its hypervascularization. Improving the efficiency of anti-angiogenic treatment and mitigation of anti-angiogenic drug resistance are the top priorities in the development of non-surgical HCC therapies. Endoglin (CD105), a transmembrane glycoprotein, is one of the transforming growth factor β (TGF-β) co-receptors. Involvement of that protein in angiogenesis of solid tumours is well documented. Endoglin is a marker of activated endothelial cells (ECs), and is preferentially expressed in the angiogenic endothelium of solid tumours, including HCC. HCC is associated with changes in CD105-positive ECs within and around the tumour. The large spectrum of endoglin effects in the liver is cell-type- and HCC- stage-specific. High expression of endoglin in non-tumour tissue suggests that this microenvironment might play an especially important role in the progression of HCC. Evaluation of tissue expression, as well as serum concentrations of this glycoprotein in HCC, tends to confirm its role as an important biomarker in HCC diagnosis and prognosis. The role of endoglin in liver fibrosis and HCC progression also makes it an attractive therapeutic target. Despite these facts, the exact molecular mechanisms of endoglin functioning in hepatocarcinogenesis are still poorly understood. This review summarizes the current data concerning the role and signalling pathways of endoglin in hepatocellular carcinoma development and progression, and provides an overview of the strategies available for a specific targeting of CD105 in anti-angiogenic therapy in HCC. MDPI 2018-12-05 /pmc/articles/PMC6321450/ /pubmed/30563158 http://dx.doi.org/10.3390/ijms19123887 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Kasprzak, Aldona
Adamek, Agnieszka
Role of Endoglin (CD105) in the Progression of Hepatocellular Carcinoma and Anti-Angiogenic Therapy
title Role of Endoglin (CD105) in the Progression of Hepatocellular Carcinoma and Anti-Angiogenic Therapy
title_full Role of Endoglin (CD105) in the Progression of Hepatocellular Carcinoma and Anti-Angiogenic Therapy
title_fullStr Role of Endoglin (CD105) in the Progression of Hepatocellular Carcinoma and Anti-Angiogenic Therapy
title_full_unstemmed Role of Endoglin (CD105) in the Progression of Hepatocellular Carcinoma and Anti-Angiogenic Therapy
title_short Role of Endoglin (CD105) in the Progression of Hepatocellular Carcinoma and Anti-Angiogenic Therapy
title_sort role of endoglin (cd105) in the progression of hepatocellular carcinoma and anti-angiogenic therapy
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6321450/
https://www.ncbi.nlm.nih.gov/pubmed/30563158
http://dx.doi.org/10.3390/ijms19123887
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