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LRP-1 Matricellular Receptor Involvement in Triple Negative Breast Cancer Tumor Angiogenesis
Background: LRP-1 is a multifunctional scavenger receptor belonging to the LDLR family. Due to its capacity to control pericellular levels of various growth factors and proteases, LRP-1 plays a crucial role in membrane proteome dynamics, which appears decisive for tumor progression. Methods: LRP-1 i...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8533426/ https://www.ncbi.nlm.nih.gov/pubmed/34680548 http://dx.doi.org/10.3390/biomedicines9101430 |
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author | Campion, Océane Thevenard Devy, Jessica Billottet, Clotilde Schneider, Christophe Etique, Nicolas Dupuy, Jean-William Raymond, Anne-Aurélie Boulagnon Rombi, Camille Meunier, Marie Djermoune, El-Hadi Lelièvre, Elodie Wahart, Amandine Bour, Camille Hachet, Cathy Cairo, Stefano Bikfalvi, Andréas Dedieu, Stéphane Devy, Jérôme |
author_facet | Campion, Océane Thevenard Devy, Jessica Billottet, Clotilde Schneider, Christophe Etique, Nicolas Dupuy, Jean-William Raymond, Anne-Aurélie Boulagnon Rombi, Camille Meunier, Marie Djermoune, El-Hadi Lelièvre, Elodie Wahart, Amandine Bour, Camille Hachet, Cathy Cairo, Stefano Bikfalvi, Andréas Dedieu, Stéphane Devy, Jérôme |
author_sort | Campion, Océane |
collection | PubMed |
description | Background: LRP-1 is a multifunctional scavenger receptor belonging to the LDLR family. Due to its capacity to control pericellular levels of various growth factors and proteases, LRP-1 plays a crucial role in membrane proteome dynamics, which appears decisive for tumor progression. Methods: LRP-1 involvement in a TNBC model was assessed using an RNA interference strategy in MDA-MB-231 cells. In vivo, tumorigenic and angiogenic effects of LRP-1-repressed cells were evaluated using an orthotopic xenograft model and two angiogenic assays (Matrigel(®) plugs, CAM). DCE-MRI, FMT, and IHC were used to complete a tumor longitudinal follow-up and obtain morphological and functional vascular information. In vitro, HUVECs’ angiogenic potential was evaluated using a tumor secretome, subjected to a proteomic analysis to highlight LRP-1-dependant signaling pathways. Results: LRP-1 repression in MDA-MB-231 tumors led to a 60% growth delay because of, inter alia, morphological and functional vascular differences, confirmed by angiogenic models. In vitro, the LRP-1-repressed cells secretome restrained HUVECs’ angiogenic capabilities. A proteomics analysis revealed that LRP-1 supports tumor growth and angiogenesis by regulating TGF-β signaling and plasminogen/plasmin system. Conclusions: LRP-1, by its wide spectrum of interactions, emerges as an important matricellular player in the control of cancer-signaling events such as angiogenesis, by supporting tumor vascular morphology and functionality. |
format | Online Article Text |
id | pubmed-8533426 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-85334262021-10-23 LRP-1 Matricellular Receptor Involvement in Triple Negative Breast Cancer Tumor Angiogenesis Campion, Océane Thevenard Devy, Jessica Billottet, Clotilde Schneider, Christophe Etique, Nicolas Dupuy, Jean-William Raymond, Anne-Aurélie Boulagnon Rombi, Camille Meunier, Marie Djermoune, El-Hadi Lelièvre, Elodie Wahart, Amandine Bour, Camille Hachet, Cathy Cairo, Stefano Bikfalvi, Andréas Dedieu, Stéphane Devy, Jérôme Biomedicines Article Background: LRP-1 is a multifunctional scavenger receptor belonging to the LDLR family. Due to its capacity to control pericellular levels of various growth factors and proteases, LRP-1 plays a crucial role in membrane proteome dynamics, which appears decisive for tumor progression. Methods: LRP-1 involvement in a TNBC model was assessed using an RNA interference strategy in MDA-MB-231 cells. In vivo, tumorigenic and angiogenic effects of LRP-1-repressed cells were evaluated using an orthotopic xenograft model and two angiogenic assays (Matrigel(®) plugs, CAM). DCE-MRI, FMT, and IHC were used to complete a tumor longitudinal follow-up and obtain morphological and functional vascular information. In vitro, HUVECs’ angiogenic potential was evaluated using a tumor secretome, subjected to a proteomic analysis to highlight LRP-1-dependant signaling pathways. Results: LRP-1 repression in MDA-MB-231 tumors led to a 60% growth delay because of, inter alia, morphological and functional vascular differences, confirmed by angiogenic models. In vitro, the LRP-1-repressed cells secretome restrained HUVECs’ angiogenic capabilities. A proteomics analysis revealed that LRP-1 supports tumor growth and angiogenesis by regulating TGF-β signaling and plasminogen/plasmin system. Conclusions: LRP-1, by its wide spectrum of interactions, emerges as an important matricellular player in the control of cancer-signaling events such as angiogenesis, by supporting tumor vascular morphology and functionality. MDPI 2021-10-09 /pmc/articles/PMC8533426/ /pubmed/34680548 http://dx.doi.org/10.3390/biomedicines9101430 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 Campion, Océane Thevenard Devy, Jessica Billottet, Clotilde Schneider, Christophe Etique, Nicolas Dupuy, Jean-William Raymond, Anne-Aurélie Boulagnon Rombi, Camille Meunier, Marie Djermoune, El-Hadi Lelièvre, Elodie Wahart, Amandine Bour, Camille Hachet, Cathy Cairo, Stefano Bikfalvi, Andréas Dedieu, Stéphane Devy, Jérôme LRP-1 Matricellular Receptor Involvement in Triple Negative Breast Cancer Tumor Angiogenesis |
title | LRP-1 Matricellular Receptor Involvement in Triple Negative Breast Cancer Tumor Angiogenesis |
title_full | LRP-1 Matricellular Receptor Involvement in Triple Negative Breast Cancer Tumor Angiogenesis |
title_fullStr | LRP-1 Matricellular Receptor Involvement in Triple Negative Breast Cancer Tumor Angiogenesis |
title_full_unstemmed | LRP-1 Matricellular Receptor Involvement in Triple Negative Breast Cancer Tumor Angiogenesis |
title_short | LRP-1 Matricellular Receptor Involvement in Triple Negative Breast Cancer Tumor Angiogenesis |
title_sort | lrp-1 matricellular receptor involvement in triple negative breast cancer tumor angiogenesis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8533426/ https://www.ncbi.nlm.nih.gov/pubmed/34680548 http://dx.doi.org/10.3390/biomedicines9101430 |
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