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

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Institute of Physiological Chemistry and Pathobiochemistry, University of Münster, 48149 Münster, Germany
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Luis Costa Lab, Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, 1649-028 Lisboa, Portugal
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Department of Cell and Developmental Biology, Flow Cytometry Unit, Max Planck Institute for Molecular Biomedicine, 48149 Münster, Germany
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Department of Vascular Cell Biology, Max Planck-Institute of Molecular Biomedicine, 48149 Münster, Germany
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European Institute for Molecular Imaging (EIMI), University of Münster, 48149 Münster, Germany
*
Author to whom correspondence should be addressed.
Cancers 2020, 12(8), 2138; https://doi.org/10.3390/cancers12082138
Received: 2 July 2020 / Revised: 29 July 2020 / Accepted: 30 July 2020 / Published: 1 August 2020
(This article belongs to the Section Tumor Microenvironment)
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. View Full-Text
Keywords: breast cancer; human umbilical vein endothelial cells (HUVEC); epithelial-mesenchymal transition (EMT); cadherin switching; extracellular vesicles (EVs); invasion; vascular mimicry (VM) breast cancer; human umbilical vein endothelial cells (HUVEC); epithelial-mesenchymal transition (EMT); cadherin switching; extracellular vesicles (EVs); invasion; vascular mimicry (VM)
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MDPI and ACS Style

Rezaei, M.; Martins Cavaco, A.C.; Stehling, M.; Nottebaum, A.; Brockhaus, K.; Caliandro, M.F.; Schelhaas, S.; Schmalbein, F.; Vestweber, D.; Eble, J.A. Extracellular Vesicle Transfer from Endothelial Cells Drives VE-Cadherin Expression in Breast Cancer Cells, Thereby Causing Heterotypic Cell Contacts. Cancers 2020, 12, 2138. https://doi.org/10.3390/cancers12082138

AMA Style

Rezaei M, Martins Cavaco AC, Stehling M, Nottebaum A, Brockhaus K, Caliandro MF, Schelhaas S, Schmalbein F, Vestweber D, Eble JA. Extracellular Vesicle Transfer from Endothelial Cells Drives VE-Cadherin Expression in Breast Cancer Cells, Thereby Causing Heterotypic Cell Contacts. Cancers. 2020; 12(8):2138. https://doi.org/10.3390/cancers12082138

Chicago/Turabian Style

Rezaei, Maryam, Ana C. Martins Cavaco, Martin Stehling, Astrid Nottebaum, Katrin Brockhaus, Michele F. Caliandro, Sonja Schelhaas, Felix Schmalbein, Dietmar Vestweber, and Johannes A. Eble 2020. "Extracellular Vesicle Transfer from Endothelial Cells Drives VE-Cadherin Expression in Breast Cancer Cells, Thereby Causing Heterotypic Cell Contacts" Cancers 12, no. 8: 2138. https://doi.org/10.3390/cancers12082138

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