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The Influence of VE-Cadherin on Adhesion and Incorporation of Breast Cancer Cells into Vascular Endothelium

During metastasis, cancer cells that originate from the primary tumor circulate in the bloodstream, extravasate, and form micrometastases at distant locations. Several lines of evidence suggest that specific interactions between cancer cells and endothelial cells, in particular tumor cell adhesion t...

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Autores principales: Brock, Thomas, Boudriot, Elisabeth, Klawitter, Anke, Großer, Marianne, Nguyen, Trang T. P., Giebe, Sindy, Klapproth, Erik, Temme, Achim, El-Armouche, Ali, Breier, Georg
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8199973/
https://www.ncbi.nlm.nih.gov/pubmed/34205118
http://dx.doi.org/10.3390/ijms22116049
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author Brock, Thomas
Boudriot, Elisabeth
Klawitter, Anke
Großer, Marianne
Nguyen, Trang T. P.
Giebe, Sindy
Klapproth, Erik
Temme, Achim
El-Armouche, Ali
Breier, Georg
author_facet Brock, Thomas
Boudriot, Elisabeth
Klawitter, Anke
Großer, Marianne
Nguyen, Trang T. P.
Giebe, Sindy
Klapproth, Erik
Temme, Achim
El-Armouche, Ali
Breier, Georg
author_sort Brock, Thomas
collection PubMed
description During metastasis, cancer cells that originate from the primary tumor circulate in the bloodstream, extravasate, and form micrometastases at distant locations. Several lines of evidence suggest that specific interactions between cancer cells and endothelial cells, in particular tumor cell adhesion to the endothelium and transendothelial migration, play a crucial role in extravasation. Here we have studied the role of vascular endothelial (VE)-cadherin which is expressed aberrantly by breast cancer cells and might promote such interactions. By comparing different human breast cancer cell lines, we observed that the number of cancer cells that adhered to endothelium correlated with VE-cadherin expression levels. VE-cadherin silencing experiments confirmed that VE-cadherin enhances cancer cell adhesion to endothelial cells. However, in contrast, the number of cancer cells that incorporated into the endothelium was not dependent on VE-cadherin. Thus, it appears that cancer cell adhesion and incorporation are distinct processes that are governed by different molecular mechanisms. When cancer cells incorporated into the endothelial monolayer, they formed VE-cadherin positive contacts with endothelial cells. On the other hand, we also observed tumor cells that had displaced endothelial cells, reflecting either different modes of incorporation, or a temporal sequence where cancer cells first form contact with endothelial cells and then displace them to facilitate transmigration. Taken together, these results show that VE-cadherin promotes the adhesion of breast cancer cells to the endothelium and is involved in the initial phase of incorporation, but not their transmigration. Thus, VE-cadherin might be of relevance for therapeutic strategies aiming at preventing the metastatic spread of breast cancer cells.
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spelling pubmed-81999732021-06-14 The Influence of VE-Cadherin on Adhesion and Incorporation of Breast Cancer Cells into Vascular Endothelium Brock, Thomas Boudriot, Elisabeth Klawitter, Anke Großer, Marianne Nguyen, Trang T. P. Giebe, Sindy Klapproth, Erik Temme, Achim El-Armouche, Ali Breier, Georg Int J Mol Sci Article During metastasis, cancer cells that originate from the primary tumor circulate in the bloodstream, extravasate, and form micrometastases at distant locations. Several lines of evidence suggest that specific interactions between cancer cells and endothelial cells, in particular tumor cell adhesion to the endothelium and transendothelial migration, play a crucial role in extravasation. Here we have studied the role of vascular endothelial (VE)-cadherin which is expressed aberrantly by breast cancer cells and might promote such interactions. By comparing different human breast cancer cell lines, we observed that the number of cancer cells that adhered to endothelium correlated with VE-cadherin expression levels. VE-cadherin silencing experiments confirmed that VE-cadherin enhances cancer cell adhesion to endothelial cells. However, in contrast, the number of cancer cells that incorporated into the endothelium was not dependent on VE-cadherin. Thus, it appears that cancer cell adhesion and incorporation are distinct processes that are governed by different molecular mechanisms. When cancer cells incorporated into the endothelial monolayer, they formed VE-cadherin positive contacts with endothelial cells. On the other hand, we also observed tumor cells that had displaced endothelial cells, reflecting either different modes of incorporation, or a temporal sequence where cancer cells first form contact with endothelial cells and then displace them to facilitate transmigration. Taken together, these results show that VE-cadherin promotes the adhesion of breast cancer cells to the endothelium and is involved in the initial phase of incorporation, but not their transmigration. Thus, VE-cadherin might be of relevance for therapeutic strategies aiming at preventing the metastatic spread of breast cancer cells. MDPI 2021-06-03 /pmc/articles/PMC8199973/ /pubmed/34205118 http://dx.doi.org/10.3390/ijms22116049 Text en © 2021 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
Brock, Thomas
Boudriot, Elisabeth
Klawitter, Anke
Großer, Marianne
Nguyen, Trang T. P.
Giebe, Sindy
Klapproth, Erik
Temme, Achim
El-Armouche, Ali
Breier, Georg
The Influence of VE-Cadherin on Adhesion and Incorporation of Breast Cancer Cells into Vascular Endothelium
title The Influence of VE-Cadherin on Adhesion and Incorporation of Breast Cancer Cells into Vascular Endothelium
title_full The Influence of VE-Cadherin on Adhesion and Incorporation of Breast Cancer Cells into Vascular Endothelium
title_fullStr The Influence of VE-Cadherin on Adhesion and Incorporation of Breast Cancer Cells into Vascular Endothelium
title_full_unstemmed The Influence of VE-Cadherin on Adhesion and Incorporation of Breast Cancer Cells into Vascular Endothelium
title_short The Influence of VE-Cadherin on Adhesion and Incorporation of Breast Cancer Cells into Vascular Endothelium
title_sort influence of ve-cadherin on adhesion and incorporation of breast cancer cells into vascular endothelium
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8199973/
https://www.ncbi.nlm.nih.gov/pubmed/34205118
http://dx.doi.org/10.3390/ijms22116049
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