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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...

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Autores principales: Sathiyanadan, Karthik, Alonso, Florian, Domingos-Pereira, Sonia, Santoro, Tania, Hamard, Lauriane, Cesson, Valérie, Meda, Paolo, Nardelli-Haefliger, Denise, Haefliger, Jacques-Antoine
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
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.
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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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