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Extracellular Vesicle Transfer from Endothelial Cells Drives VE-Cadherin Expression in Breast Cancer Cells, Thereby Causing Heterotypic Cell Contacts

Cadherins mediate cohesive contacts between isotypic cells by homophilic interaction and prevent contact between heterotypic cells. Breast cancer cells neighboring endothelial cells (ECs) atypically express vascular endothelial (VE)-cadherin. To understand this EC-induced VE-cadherin expression in b...

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Autores principales: Rezaei, Maryam, Martins Cavaco, Ana C., Stehling, Martin, Nottebaum, Astrid, Brockhaus, Katrin, Caliandro, Michele F., Schelhaas, Sonja, Schmalbein, Felix, Vestweber, Dietmar, Eble, Johannes A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7463713/
https://www.ncbi.nlm.nih.gov/pubmed/32752204
http://dx.doi.org/10.3390/cancers12082138
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author Rezaei, Maryam
Martins Cavaco, Ana C.
Stehling, Martin
Nottebaum, Astrid
Brockhaus, Katrin
Caliandro, Michele F.
Schelhaas, Sonja
Schmalbein, Felix
Vestweber, Dietmar
Eble, Johannes A.
author_facet Rezaei, Maryam
Martins Cavaco, Ana C.
Stehling, Martin
Nottebaum, Astrid
Brockhaus, Katrin
Caliandro, Michele F.
Schelhaas, Sonja
Schmalbein, Felix
Vestweber, Dietmar
Eble, Johannes A.
author_sort Rezaei, Maryam
collection PubMed
description Cadherins mediate cohesive contacts between isotypic cells by homophilic interaction and prevent contact between heterotypic cells. Breast cancer cells neighboring endothelial cells (ECs) atypically express vascular endothelial (VE)-cadherin. To understand this EC-induced VE-cadherin expression in breast cancer cells, MCF7 and MDA-MB-231 cells expressing different endogenous cadherins were co-cultured with ECs and analyzed for VE-cadherin at the transcriptional level and by confocal microscopy, flow cytometry, and immunoblotting. After losing their endogenous cadherins and neo-expression of VE-cadherin, these cells integrated into an EC monolayer without compromising the barrier function instantly. However, they induced the death of nearby ECs. EC-derived extracellular vesicles (EVs) contained soluble and membrane-anchored forms of VE-cadherin. Only the latter was re-utilized by the cancer cells. In a reporter gene assay, EC-adjacent cancer cells also showed a juxtacrine but no paracrine activation of the endogenous VE-cadherin gene. This cadherin switch enabled intimate contact between cancer and endothelial cells in a chicken chorioallantoic membrane tumor model showing vasculogenic mimicry (VM). This EV-mediated, EC-induced cadherin switch in breast cancer cells and the neo-expression of VE-cadherin mechanistically explain the mutual communication in the tumor microenvironment. Hence, it may be a target to tackle VM, which is often found in breast cancers of poor prognosis.
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spelling pubmed-74637132020-09-02 Extracellular Vesicle Transfer from Endothelial Cells Drives VE-Cadherin Expression in Breast Cancer Cells, Thereby Causing Heterotypic Cell Contacts Rezaei, Maryam Martins Cavaco, Ana C. Stehling, Martin Nottebaum, Astrid Brockhaus, Katrin Caliandro, Michele F. Schelhaas, Sonja Schmalbein, Felix Vestweber, Dietmar Eble, Johannes A. Cancers (Basel) Article Cadherins mediate cohesive contacts between isotypic cells by homophilic interaction and prevent contact between heterotypic cells. Breast cancer cells neighboring endothelial cells (ECs) atypically express vascular endothelial (VE)-cadherin. To understand this EC-induced VE-cadherin expression in breast cancer cells, MCF7 and MDA-MB-231 cells expressing different endogenous cadherins were co-cultured with ECs and analyzed for VE-cadherin at the transcriptional level and by confocal microscopy, flow cytometry, and immunoblotting. After losing their endogenous cadherins and neo-expression of VE-cadherin, these cells integrated into an EC monolayer without compromising the barrier function instantly. However, they induced the death of nearby ECs. EC-derived extracellular vesicles (EVs) contained soluble and membrane-anchored forms of VE-cadherin. Only the latter was re-utilized by the cancer cells. In a reporter gene assay, EC-adjacent cancer cells also showed a juxtacrine but no paracrine activation of the endogenous VE-cadherin gene. This cadherin switch enabled intimate contact between cancer and endothelial cells in a chicken chorioallantoic membrane tumor model showing vasculogenic mimicry (VM). This EV-mediated, EC-induced cadherin switch in breast cancer cells and the neo-expression of VE-cadherin mechanistically explain the mutual communication in the tumor microenvironment. Hence, it may be a target to tackle VM, which is often found in breast cancers of poor prognosis. MDPI 2020-08-01 /pmc/articles/PMC7463713/ /pubmed/32752204 http://dx.doi.org/10.3390/cancers12082138 Text en © 2020 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
Rezaei, Maryam
Martins Cavaco, Ana C.
Stehling, Martin
Nottebaum, Astrid
Brockhaus, Katrin
Caliandro, Michele F.
Schelhaas, Sonja
Schmalbein, Felix
Vestweber, Dietmar
Eble, Johannes A.
Extracellular Vesicle Transfer from Endothelial Cells Drives VE-Cadherin Expression in Breast Cancer Cells, Thereby Causing Heterotypic Cell Contacts
title Extracellular Vesicle Transfer from Endothelial Cells Drives VE-Cadherin Expression in Breast Cancer Cells, Thereby Causing Heterotypic Cell Contacts
title_full Extracellular Vesicle Transfer from Endothelial Cells Drives VE-Cadherin Expression in Breast Cancer Cells, Thereby Causing Heterotypic Cell Contacts
title_fullStr Extracellular Vesicle Transfer from Endothelial Cells Drives VE-Cadherin Expression in Breast Cancer Cells, Thereby Causing Heterotypic Cell Contacts
title_full_unstemmed Extracellular Vesicle Transfer from Endothelial Cells Drives VE-Cadherin Expression in Breast Cancer Cells, Thereby Causing Heterotypic Cell Contacts
title_short Extracellular Vesicle Transfer from Endothelial Cells Drives VE-Cadherin Expression in Breast Cancer Cells, Thereby Causing Heterotypic Cell Contacts
title_sort extracellular vesicle transfer from endothelial cells drives ve-cadherin expression in breast cancer cells, thereby causing heterotypic cell contacts
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7463713/
https://www.ncbi.nlm.nih.gov/pubmed/32752204
http://dx.doi.org/10.3390/cancers12082138
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