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Deciphering the complex role of thrombospondin-1 in glioblastoma development
We undertook a systematic study focused on the matricellular protein Thrombospondin-1 (THBS1) to uncover molecular mechanisms underlying the role of THBS1 in glioblastoma (GBM) development. THBS1 was found to be increased with glioma grades. Mechanistically, we show that the TGFβ canonical pathway t...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6408502/ https://www.ncbi.nlm.nih.gov/pubmed/30850588 http://dx.doi.org/10.1038/s41467-019-08480-y |
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author | Daubon, Thomas Léon, Céline Clarke, Kim Andrique, Laetitia Salabert, Laura Darbo, Elodie Pineau, Raphael Guérit, Sylvaine Maitre, Marlène Dedieu, Stéphane Jeanne, Albin Bailly, Sabine Feige, Jean-Jacques Miletic, Hrvoje Rossi, Marco Bello, Lorenzo Falciani, Francesco Bjerkvig, Rolf Bikfalvi, Andréas |
author_facet | Daubon, Thomas Léon, Céline Clarke, Kim Andrique, Laetitia Salabert, Laura Darbo, Elodie Pineau, Raphael Guérit, Sylvaine Maitre, Marlène Dedieu, Stéphane Jeanne, Albin Bailly, Sabine Feige, Jean-Jacques Miletic, Hrvoje Rossi, Marco Bello, Lorenzo Falciani, Francesco Bjerkvig, Rolf Bikfalvi, Andréas |
author_sort | Daubon, Thomas |
collection | PubMed |
description | We undertook a systematic study focused on the matricellular protein Thrombospondin-1 (THBS1) to uncover molecular mechanisms underlying the role of THBS1 in glioblastoma (GBM) development. THBS1 was found to be increased with glioma grades. Mechanistically, we show that the TGFβ canonical pathway transcriptionally regulates THBS1, through SMAD3 binding to the THBS1 gene promoter. THBS1 silencing inhibits tumour cell invasion and growth, alone and in combination with anti-angiogenic therapy. Specific inhibition of the THBS1/CD47 interaction using an antagonist peptide decreases cell invasion. This is confirmed by CD47 knock-down experiments. RNA sequencing of patient-derived xenograft tissue from laser capture micro-dissected peripheral and central tumour areas demonstrates that THBS1 is one of the gene with the highest connectivity at the tumour borders. All in all, these data show that TGFβ1 induces THBS1 expression via Smad3 which contributes to the invasive behaviour during GBM expansion. Furthermore, tumour cell-bound CD47 is implicated in this process. |
format | Online Article Text |
id | pubmed-6408502 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-64085022019-03-11 Deciphering the complex role of thrombospondin-1 in glioblastoma development Daubon, Thomas Léon, Céline Clarke, Kim Andrique, Laetitia Salabert, Laura Darbo, Elodie Pineau, Raphael Guérit, Sylvaine Maitre, Marlène Dedieu, Stéphane Jeanne, Albin Bailly, Sabine Feige, Jean-Jacques Miletic, Hrvoje Rossi, Marco Bello, Lorenzo Falciani, Francesco Bjerkvig, Rolf Bikfalvi, Andréas Nat Commun Article We undertook a systematic study focused on the matricellular protein Thrombospondin-1 (THBS1) to uncover molecular mechanisms underlying the role of THBS1 in glioblastoma (GBM) development. THBS1 was found to be increased with glioma grades. Mechanistically, we show that the TGFβ canonical pathway transcriptionally regulates THBS1, through SMAD3 binding to the THBS1 gene promoter. THBS1 silencing inhibits tumour cell invasion and growth, alone and in combination with anti-angiogenic therapy. Specific inhibition of the THBS1/CD47 interaction using an antagonist peptide decreases cell invasion. This is confirmed by CD47 knock-down experiments. RNA sequencing of patient-derived xenograft tissue from laser capture micro-dissected peripheral and central tumour areas demonstrates that THBS1 is one of the gene with the highest connectivity at the tumour borders. All in all, these data show that TGFβ1 induces THBS1 expression via Smad3 which contributes to the invasive behaviour during GBM expansion. Furthermore, tumour cell-bound CD47 is implicated in this process. Nature Publishing Group UK 2019-03-08 /pmc/articles/PMC6408502/ /pubmed/30850588 http://dx.doi.org/10.1038/s41467-019-08480-y Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Daubon, Thomas Léon, Céline Clarke, Kim Andrique, Laetitia Salabert, Laura Darbo, Elodie Pineau, Raphael Guérit, Sylvaine Maitre, Marlène Dedieu, Stéphane Jeanne, Albin Bailly, Sabine Feige, Jean-Jacques Miletic, Hrvoje Rossi, Marco Bello, Lorenzo Falciani, Francesco Bjerkvig, Rolf Bikfalvi, Andréas Deciphering the complex role of thrombospondin-1 in glioblastoma development |
title | Deciphering the complex role of thrombospondin-1 in glioblastoma development |
title_full | Deciphering the complex role of thrombospondin-1 in glioblastoma development |
title_fullStr | Deciphering the complex role of thrombospondin-1 in glioblastoma development |
title_full_unstemmed | Deciphering the complex role of thrombospondin-1 in glioblastoma development |
title_short | Deciphering the complex role of thrombospondin-1 in glioblastoma development |
title_sort | deciphering the complex role of thrombospondin-1 in glioblastoma development |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6408502/ https://www.ncbi.nlm.nih.gov/pubmed/30850588 http://dx.doi.org/10.1038/s41467-019-08480-y |
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