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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...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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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). |
format | Online Article Text |
id | pubmed-7016878 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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