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Targeting Endothelial Connexin37 Reduces Angiogenesis and Decreases Tumor Growth
Connexin37 (Cx37) and Cx40 form intercellular channels between endothelial cells (EC), which contribute to the regulation of the functions of vessels. We previously documented the participation of both Cx in developmental angiogenesis and have further shown that loss of Cx40 decreases the growth of...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8948817/ https://www.ncbi.nlm.nih.gov/pubmed/35328350 http://dx.doi.org/10.3390/ijms23062930 |
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author | Sathiyanadan, Karthik Alonso, Florian Domingos-Pereira, Sonia Santoro, Tania Hamard, Lauriane Cesson, Valérie Meda, Paolo Nardelli-Haefliger, Denise Haefliger, Jacques-Antoine |
author_facet | Sathiyanadan, Karthik Alonso, Florian Domingos-Pereira, Sonia Santoro, Tania Hamard, Lauriane Cesson, Valérie Meda, Paolo Nardelli-Haefliger, Denise Haefliger, Jacques-Antoine |
author_sort | Sathiyanadan, Karthik |
collection | PubMed |
description | Connexin37 (Cx37) and Cx40 form intercellular channels between endothelial cells (EC), which contribute to the regulation of the functions of vessels. We previously documented the participation of both Cx in developmental angiogenesis and have further shown that loss of Cx40 decreases the growth of different tumors. Here, we report that loss of Cx37 reduces (1) the in vitro proliferation of primary human EC; (2) the vascularization of subcutaneously implanted matrigel plugs in Cx37−/− mice or in WT using matrigel plugs supplemented with a peptide targeting Cx37 channels; (3) tumor angiogenesis; and (4) the growth of TC-1 and B16 tumors, resulting in a longer mice survival. We further document that Cx37 and Cx40 function in a collaborative manner to promote tumor growth, inasmuch as the injection of a peptide targeting Cx40 into Cx37−/− mice decreased the growth of TC-1 tumors to a larger extent than after loss of Cx37. This loss did not alter vessel perfusion, mural cells coverage and tumor hypoxia compared to tumors grown in WT mice. The data show that Cx37 is relevant for the control of EC proliferation and growth in different tumor models, suggesting that it may be a target, alone or in combination with Cx40, in the development of anti-tumoral treatments. |
format | Online Article Text |
id | pubmed-8948817 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-89488172022-03-26 Targeting Endothelial Connexin37 Reduces Angiogenesis and Decreases Tumor Growth Sathiyanadan, Karthik Alonso, Florian Domingos-Pereira, Sonia Santoro, Tania Hamard, Lauriane Cesson, Valérie Meda, Paolo Nardelli-Haefliger, Denise Haefliger, Jacques-Antoine Int J Mol Sci Article Connexin37 (Cx37) and Cx40 form intercellular channels between endothelial cells (EC), which contribute to the regulation of the functions of vessels. We previously documented the participation of both Cx in developmental angiogenesis and have further shown that loss of Cx40 decreases the growth of different tumors. Here, we report that loss of Cx37 reduces (1) the in vitro proliferation of primary human EC; (2) the vascularization of subcutaneously implanted matrigel plugs in Cx37−/− mice or in WT using matrigel plugs supplemented with a peptide targeting Cx37 channels; (3) tumor angiogenesis; and (4) the growth of TC-1 and B16 tumors, resulting in a longer mice survival. We further document that Cx37 and Cx40 function in a collaborative manner to promote tumor growth, inasmuch as the injection of a peptide targeting Cx40 into Cx37−/− mice decreased the growth of TC-1 tumors to a larger extent than after loss of Cx37. This loss did not alter vessel perfusion, mural cells coverage and tumor hypoxia compared to tumors grown in WT mice. The data show that Cx37 is relevant for the control of EC proliferation and growth in different tumor models, suggesting that it may be a target, alone or in combination with Cx40, in the development of anti-tumoral treatments. MDPI 2022-03-08 /pmc/articles/PMC8948817/ /pubmed/35328350 http://dx.doi.org/10.3390/ijms23062930 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Sathiyanadan, Karthik Alonso, Florian Domingos-Pereira, Sonia Santoro, Tania Hamard, Lauriane Cesson, Valérie Meda, Paolo Nardelli-Haefliger, Denise Haefliger, Jacques-Antoine Targeting Endothelial Connexin37 Reduces Angiogenesis and Decreases Tumor Growth |
title | Targeting Endothelial Connexin37 Reduces Angiogenesis and Decreases Tumor Growth |
title_full | Targeting Endothelial Connexin37 Reduces Angiogenesis and Decreases Tumor Growth |
title_fullStr | Targeting Endothelial Connexin37 Reduces Angiogenesis and Decreases Tumor Growth |
title_full_unstemmed | Targeting Endothelial Connexin37 Reduces Angiogenesis and Decreases Tumor Growth |
title_short | Targeting Endothelial Connexin37 Reduces Angiogenesis and Decreases Tumor Growth |
title_sort | targeting endothelial connexin37 reduces angiogenesis and decreases tumor growth |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8948817/ https://www.ncbi.nlm.nih.gov/pubmed/35328350 http://dx.doi.org/10.3390/ijms23062930 |
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