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Periostin Secreted by Glioblastoma Stem Cells Recruits M2 Tumor-associated Macrophages and Promotes Malignant Growth
Tumor-associated macrophages (TAMs) are enriched in glioblastoma (GBM) that contains glioma stem cells (GSCs) at the apex of its cellular hierarchy. The correlation between TAM density and glioma grade suggests a supportive role of TAMs in tumor progression. Here we interrogated the molecular link b...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4312504/ https://www.ncbi.nlm.nih.gov/pubmed/25580734 http://dx.doi.org/10.1038/ncb3090 |
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author | Zhou, Wenchao Ke, Susan Q. Huang, Zhi Flavahan, William Fang, Xiaoguang Paul, Jeremy Wu, Ling Sloan, Andrew E. McLendon, Roger E. Li, Xiaoxia Rich, Jeremy N. Bao, Shideng |
author_facet | Zhou, Wenchao Ke, Susan Q. Huang, Zhi Flavahan, William Fang, Xiaoguang Paul, Jeremy Wu, Ling Sloan, Andrew E. McLendon, Roger E. Li, Xiaoxia Rich, Jeremy N. Bao, Shideng |
author_sort | Zhou, Wenchao |
collection | PubMed |
description | Tumor-associated macrophages (TAMs) are enriched in glioblastoma (GBM) that contains glioma stem cells (GSCs) at the apex of its cellular hierarchy. The correlation between TAM density and glioma grade suggests a supportive role of TAMs in tumor progression. Here we interrogated the molecular link between GSCs and TAM recruitment in GBMs and demonstrated that GSCs secrete Periostin (POSTN) to recruit TAMs. TAM density correlates with POSTN levels in human GBMs. Silencing POSTN in GSCs markedly reduced TAM density, inhibited tumor growth, and increased survival of mice bearing GSC-derived xenografts. We found that TAMs in GBMs are not brain-resident microglia, but mainly monocyte-derived macrophages from peripheral blood. Disrupting POSTN specifically attenuated the tumor supportive M2 type of TAMs in xenografts. POSTN recruits TAMs through integrin α(v)β(3) as blocking this signaling by an RGD peptide inhibited TAM recruitment. Our findings highlight the possibility of improving GBM treatment by targeting POSTN-mediated TAM recruitment. |
format | Online Article Text |
id | pubmed-4312504 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
record_format | MEDLINE/PubMed |
spelling | pubmed-43125042015-08-01 Periostin Secreted by Glioblastoma Stem Cells Recruits M2 Tumor-associated Macrophages and Promotes Malignant Growth Zhou, Wenchao Ke, Susan Q. Huang, Zhi Flavahan, William Fang, Xiaoguang Paul, Jeremy Wu, Ling Sloan, Andrew E. McLendon, Roger E. Li, Xiaoxia Rich, Jeremy N. Bao, Shideng Nat Cell Biol Article Tumor-associated macrophages (TAMs) are enriched in glioblastoma (GBM) that contains glioma stem cells (GSCs) at the apex of its cellular hierarchy. The correlation between TAM density and glioma grade suggests a supportive role of TAMs in tumor progression. Here we interrogated the molecular link between GSCs and TAM recruitment in GBMs and demonstrated that GSCs secrete Periostin (POSTN) to recruit TAMs. TAM density correlates with POSTN levels in human GBMs. Silencing POSTN in GSCs markedly reduced TAM density, inhibited tumor growth, and increased survival of mice bearing GSC-derived xenografts. We found that TAMs in GBMs are not brain-resident microglia, but mainly monocyte-derived macrophages from peripheral blood. Disrupting POSTN specifically attenuated the tumor supportive M2 type of TAMs in xenografts. POSTN recruits TAMs through integrin α(v)β(3) as blocking this signaling by an RGD peptide inhibited TAM recruitment. Our findings highlight the possibility of improving GBM treatment by targeting POSTN-mediated TAM recruitment. 2015-01-12 2015-02 /pmc/articles/PMC4312504/ /pubmed/25580734 http://dx.doi.org/10.1038/ncb3090 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Zhou, Wenchao Ke, Susan Q. Huang, Zhi Flavahan, William Fang, Xiaoguang Paul, Jeremy Wu, Ling Sloan, Andrew E. McLendon, Roger E. Li, Xiaoxia Rich, Jeremy N. Bao, Shideng Periostin Secreted by Glioblastoma Stem Cells Recruits M2 Tumor-associated Macrophages and Promotes Malignant Growth |
title | Periostin Secreted by Glioblastoma Stem Cells Recruits M2 Tumor-associated Macrophages and Promotes Malignant Growth |
title_full | Periostin Secreted by Glioblastoma Stem Cells Recruits M2 Tumor-associated Macrophages and Promotes Malignant Growth |
title_fullStr | Periostin Secreted by Glioblastoma Stem Cells Recruits M2 Tumor-associated Macrophages and Promotes Malignant Growth |
title_full_unstemmed | Periostin Secreted by Glioblastoma Stem Cells Recruits M2 Tumor-associated Macrophages and Promotes Malignant Growth |
title_short | Periostin Secreted by Glioblastoma Stem Cells Recruits M2 Tumor-associated Macrophages and Promotes Malignant Growth |
title_sort | periostin secreted by glioblastoma stem cells recruits m2 tumor-associated macrophages and promotes malignant growth |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4312504/ https://www.ncbi.nlm.nih.gov/pubmed/25580734 http://dx.doi.org/10.1038/ncb3090 |
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