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Tumor hypoxia modulates podoplanin/CCL21 interactions in CCR7+ NK cell recruitment and CCR7+ tumor cell mobilization

Podoplanin (PDPN), an O-glycosylated, transmembrane, mucin-type glycoprotein, is expressed by cancer associated fibroblasts (CAFs). In malignant transformation, PDPN is subjected to changes and its role is yet to be established. Here we show that it is involved in modulating the activity of the CCL2...

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Autores principales: Tejchman, Anna, Lamerant-Fayel, Nathalie, Jacquinet, Jean-Claude, Bielawska-Pohl, Aleksandra, Mleczko-Sanecka, Katarzyna, Grillon, Catherine, Chouaib, Salem, Ugorski, Maciej, Kieda, Claudine
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5458255/
https://www.ncbi.nlm.nih.gov/pubmed/28416768
http://dx.doi.org/10.18632/oncotarget.16311
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author Tejchman, Anna
Lamerant-Fayel, Nathalie
Jacquinet, Jean-Claude
Bielawska-Pohl, Aleksandra
Mleczko-Sanecka, Katarzyna
Grillon, Catherine
Chouaib, Salem
Ugorski, Maciej
Kieda, Claudine
author_facet Tejchman, Anna
Lamerant-Fayel, Nathalie
Jacquinet, Jean-Claude
Bielawska-Pohl, Aleksandra
Mleczko-Sanecka, Katarzyna
Grillon, Catherine
Chouaib, Salem
Ugorski, Maciej
Kieda, Claudine
author_sort Tejchman, Anna
collection PubMed
description Podoplanin (PDPN), an O-glycosylated, transmembrane, mucin-type glycoprotein, is expressed by cancer associated fibroblasts (CAFs). In malignant transformation, PDPN is subjected to changes and its role is yet to be established. Here we show that it is involved in modulating the activity of the CCL21/CCR7 chemokine/receptor axis in a hypoxia-dependent manner. In the present model, breast cancer MDA-MB-231 cells and NKL3 cells express the surface CCR7 receptor for CCL21 chemokine which is a potent chemoattractant able to bind to PDPN. The impact of the CCL21/CCR7 axis in the molecular mechanism of the adhesion of NKL3 cells and of MDA-MB-231 breast cancer cells was reduced in a hypoxic tumor environment. In addition to its known effect on migration, CCL21/CCR7 interaction was shown to allow NK cell adhesion to endothelial cells (ECs) and its reduction by hypoxia. A PDPN expressing model of CAFs made it possible to demonstrate the same CCL21/CCR7 axis involvement in the tumor cells to CAFs recognition mechanism through PDPN binding of CCL21. PDPN was induced by hypoxia and its overexpression undergoes a reduction of adhesion, making it an anti-adhesion molecule in the absence of CCL21, in the tumor. CCL21/CCR7 modulated NK cells/ECs and MDA-MB-231 cells/CAF PDPN-dependent interactions were further shown to be linked to hypoxia-dependent microRNAs as miRs: miR-210 and specifically miR-21, miR-29b which influence PDPN expression.
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spelling pubmed-54582552017-06-08 Tumor hypoxia modulates podoplanin/CCL21 interactions in CCR7+ NK cell recruitment and CCR7+ tumor cell mobilization Tejchman, Anna Lamerant-Fayel, Nathalie Jacquinet, Jean-Claude Bielawska-Pohl, Aleksandra Mleczko-Sanecka, Katarzyna Grillon, Catherine Chouaib, Salem Ugorski, Maciej Kieda, Claudine Oncotarget Research Paper Podoplanin (PDPN), an O-glycosylated, transmembrane, mucin-type glycoprotein, is expressed by cancer associated fibroblasts (CAFs). In malignant transformation, PDPN is subjected to changes and its role is yet to be established. Here we show that it is involved in modulating the activity of the CCL21/CCR7 chemokine/receptor axis in a hypoxia-dependent manner. In the present model, breast cancer MDA-MB-231 cells and NKL3 cells express the surface CCR7 receptor for CCL21 chemokine which is a potent chemoattractant able to bind to PDPN. The impact of the CCL21/CCR7 axis in the molecular mechanism of the adhesion of NKL3 cells and of MDA-MB-231 breast cancer cells was reduced in a hypoxic tumor environment. In addition to its known effect on migration, CCL21/CCR7 interaction was shown to allow NK cell adhesion to endothelial cells (ECs) and its reduction by hypoxia. A PDPN expressing model of CAFs made it possible to demonstrate the same CCL21/CCR7 axis involvement in the tumor cells to CAFs recognition mechanism through PDPN binding of CCL21. PDPN was induced by hypoxia and its overexpression undergoes a reduction of adhesion, making it an anti-adhesion molecule in the absence of CCL21, in the tumor. CCL21/CCR7 modulated NK cells/ECs and MDA-MB-231 cells/CAF PDPN-dependent interactions were further shown to be linked to hypoxia-dependent microRNAs as miRs: miR-210 and specifically miR-21, miR-29b which influence PDPN expression. Impact Journals LLC 2017-03-17 /pmc/articles/PMC5458255/ /pubmed/28416768 http://dx.doi.org/10.18632/oncotarget.16311 Text en Copyright: © 2017 Tejchman et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) (CC-BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Tejchman, Anna
Lamerant-Fayel, Nathalie
Jacquinet, Jean-Claude
Bielawska-Pohl, Aleksandra
Mleczko-Sanecka, Katarzyna
Grillon, Catherine
Chouaib, Salem
Ugorski, Maciej
Kieda, Claudine
Tumor hypoxia modulates podoplanin/CCL21 interactions in CCR7+ NK cell recruitment and CCR7+ tumor cell mobilization
title Tumor hypoxia modulates podoplanin/CCL21 interactions in CCR7+ NK cell recruitment and CCR7+ tumor cell mobilization
title_full Tumor hypoxia modulates podoplanin/CCL21 interactions in CCR7+ NK cell recruitment and CCR7+ tumor cell mobilization
title_fullStr Tumor hypoxia modulates podoplanin/CCL21 interactions in CCR7+ NK cell recruitment and CCR7+ tumor cell mobilization
title_full_unstemmed Tumor hypoxia modulates podoplanin/CCL21 interactions in CCR7+ NK cell recruitment and CCR7+ tumor cell mobilization
title_short Tumor hypoxia modulates podoplanin/CCL21 interactions in CCR7+ NK cell recruitment and CCR7+ tumor cell mobilization
title_sort tumor hypoxia modulates podoplanin/ccl21 interactions in ccr7+ nk cell recruitment and ccr7+ tumor cell mobilization
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5458255/
https://www.ncbi.nlm.nih.gov/pubmed/28416768
http://dx.doi.org/10.18632/oncotarget.16311
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