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Angiopoietin1 Deficiency in Hepatocytes Affects the Growth of Colorectal Cancer Liver Metastases (CRCLM)

Colorectal cancer liver metastases (CRCLM) that receive their blood supply via vessel co-option are associated with a poor response to anti-angiogenic therapy. Angiopoietins (Ang1 and Ang2) with their Tyrosine-protein kinase receptor (Tie2) have been shown to support vessel co-option. We demonstrate...

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Autores principales: Ibrahim, Nisreen S., Lazaris, Anthoula, Rada, Miran, Petrillo, Stephanie K., Huck, Laurent, Hussain, Sabah, Ouladan, Shaida, Gao, Zu-Hua, Gregorieff, Alexander, Essalmani, Rachid, Seidah, Nabil G., Metrakos, Peter
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7016878/
https://www.ncbi.nlm.nih.gov/pubmed/31877668
http://dx.doi.org/10.3390/cancers12010035
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author Ibrahim, Nisreen S.
Lazaris, Anthoula
Rada, Miran
Petrillo, Stephanie K.
Huck, Laurent
Hussain, Sabah
Ouladan, Shaida
Gao, Zu-Hua
Gregorieff, Alexander
Essalmani, Rachid
Seidah, Nabil G.
Metrakos, Peter
author_facet Ibrahim, Nisreen S.
Lazaris, Anthoula
Rada, Miran
Petrillo, Stephanie K.
Huck, Laurent
Hussain, Sabah
Ouladan, Shaida
Gao, Zu-Hua
Gregorieff, Alexander
Essalmani, Rachid
Seidah, Nabil G.
Metrakos, Peter
author_sort Ibrahim, Nisreen S.
collection PubMed
description Colorectal cancer liver metastases (CRCLM) that receive their blood supply via vessel co-option are associated with a poor response to anti-angiogenic therapy. Angiopoietins (Ang1 and Ang2) with their Tyrosine-protein kinase receptor (Tie2) have been shown to support vessel co-option. We demonstrate significantly higher expression of Ang1 in hepatocytes adjacent to the tumor region of human chemonaïve and treated co-opting (replacement histopathological growth patterns: RHGP) tumors. To investigate the role of the host Ang1 expression, Ang1 knockout (KO) mice were injected intra-splenically with metastatic MC-38 colon cancer cells that develop co-opting liver metastases. We observed a reduction in the number of liver metastases and interestingly, for the first time, the development of angiogenic driven desmoplastic (DHGP) liver metastases. In addition, in-vitro, knockout of Ang1 in primary hepatocytes inhibited viability, migration and invasion ability of MC-38 cells. We also demonstrate that Ang 1 alone promotes the migration and growth of both human and mouse colon cancer cell lines These results provide evidence that high expression of Ang1 in the host liver is important to support vessel co-option (RHGP lesions) and when inhibited, favours the formation of angiogenic driven liver metastases (DHGP lesions).
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spelling pubmed-70168782020-02-28 Angiopoietin1 Deficiency in Hepatocytes Affects the Growth of Colorectal Cancer Liver Metastases (CRCLM) Ibrahim, Nisreen S. Lazaris, Anthoula Rada, Miran Petrillo, Stephanie K. Huck, Laurent Hussain, Sabah Ouladan, Shaida Gao, Zu-Hua Gregorieff, Alexander Essalmani, Rachid Seidah, Nabil G. Metrakos, Peter Cancers (Basel) Article Colorectal cancer liver metastases (CRCLM) that receive their blood supply via vessel co-option are associated with a poor response to anti-angiogenic therapy. Angiopoietins (Ang1 and Ang2) with their Tyrosine-protein kinase receptor (Tie2) have been shown to support vessel co-option. We demonstrate significantly higher expression of Ang1 in hepatocytes adjacent to the tumor region of human chemonaïve and treated co-opting (replacement histopathological growth patterns: RHGP) tumors. To investigate the role of the host Ang1 expression, Ang1 knockout (KO) mice were injected intra-splenically with metastatic MC-38 colon cancer cells that develop co-opting liver metastases. We observed a reduction in the number of liver metastases and interestingly, for the first time, the development of angiogenic driven desmoplastic (DHGP) liver metastases. In addition, in-vitro, knockout of Ang1 in primary hepatocytes inhibited viability, migration and invasion ability of MC-38 cells. We also demonstrate that Ang 1 alone promotes the migration and growth of both human and mouse colon cancer cell lines These results provide evidence that high expression of Ang1 in the host liver is important to support vessel co-option (RHGP lesions) and when inhibited, favours the formation of angiogenic driven liver metastases (DHGP lesions). MDPI 2019-12-20 /pmc/articles/PMC7016878/ /pubmed/31877668 http://dx.doi.org/10.3390/cancers12010035 Text en © 2019 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 Article
Ibrahim, Nisreen S.
Lazaris, Anthoula
Rada, Miran
Petrillo, Stephanie K.
Huck, Laurent
Hussain, Sabah
Ouladan, Shaida
Gao, Zu-Hua
Gregorieff, Alexander
Essalmani, Rachid
Seidah, Nabil G.
Metrakos, Peter
Angiopoietin1 Deficiency in Hepatocytes Affects the Growth of Colorectal Cancer Liver Metastases (CRCLM)
title Angiopoietin1 Deficiency in Hepatocytes Affects the Growth of Colorectal Cancer Liver Metastases (CRCLM)
title_full Angiopoietin1 Deficiency in Hepatocytes Affects the Growth of Colorectal Cancer Liver Metastases (CRCLM)
title_fullStr Angiopoietin1 Deficiency in Hepatocytes Affects the Growth of Colorectal Cancer Liver Metastases (CRCLM)
title_full_unstemmed Angiopoietin1 Deficiency in Hepatocytes Affects the Growth of Colorectal Cancer Liver Metastases (CRCLM)
title_short Angiopoietin1 Deficiency in Hepatocytes Affects the Growth of Colorectal Cancer Liver Metastases (CRCLM)
title_sort angiopoietin1 deficiency in hepatocytes affects the growth of colorectal cancer liver metastases (crclm)
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7016878/
https://www.ncbi.nlm.nih.gov/pubmed/31877668
http://dx.doi.org/10.3390/cancers12010035
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