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Interrogating glioma-M2 macrophage interactions identifies Gal-9/Tim-3 as a viable target against PTEN-null glioblastoma
Genomic alteration can reshape tumor microenvironment to drive tumor malignancy. However, how PTEN deficiency influences microenvironment-mediated cell-cell interactions in glioblastoma (GBM) remains unclear. Here, we show that PTEN deficiency induces a symbiotic glioma-M2 macrophage interaction to...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Association for the Advancement of Science
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9269888/ https://www.ncbi.nlm.nih.gov/pubmed/35857445 http://dx.doi.org/10.1126/sciadv.abl5165 |
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author | Ni, Xiangrong Wu, Weichi Sun, Xiaoqiang Ma, Junxiao Yu, Zhihui He, Xinwei Cheng, Jinyu Xu, Pengfei Liu, Haoxian Shang, Tengze Xi, Shaoyan Wang, Jing Zhang, Ji Chen, Zhongping |
author_facet | Ni, Xiangrong Wu, Weichi Sun, Xiaoqiang Ma, Junxiao Yu, Zhihui He, Xinwei Cheng, Jinyu Xu, Pengfei Liu, Haoxian Shang, Tengze Xi, Shaoyan Wang, Jing Zhang, Ji Chen, Zhongping |
author_sort | Ni, Xiangrong |
collection | PubMed |
description | Genomic alteration can reshape tumor microenvironment to drive tumor malignancy. However, how PTEN deficiency influences microenvironment-mediated cell-cell interactions in glioblastoma (GBM) remains unclear. Here, we show that PTEN deficiency induces a symbiotic glioma-M2 macrophage interaction to support glioma progression. Mechanistically, PTEN-deficient GBM cells secrete high levels of galectin-9 (Gal-9) via the AKT-GSK3β-IRF1 pathway. The secreted Gal-9 drives macrophage M2 polarization by activating its receptor Tim-3 and downstream pathways in macrophages. These macrophages, in turn, secrete VEGFA to stimulate angiogenesis and support glioma growth. Furthermore, enhanced Gal-9/Tim-3 expression predicts poor outcome in glioma patients. In GBM models, blockade of Gal-9/Tim-3 signaling inhibits macrophage M2 polarization and suppresses tumor growth. Moreover, α-lactose attenuates glioma angiogenesis by down-regulating macrophage-derived VEGFA, providing a novel antivascularization strategy. Therefore, our study suggests that blockade of Gal-9/Tim-3 signaling is effective to impair glioma progression by inhibiting macrophage M2 polarization, specifically for PTEN-null GBM. |
format | Online Article Text |
id | pubmed-9269888 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | American Association for the Advancement of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-92698882022-07-20 Interrogating glioma-M2 macrophage interactions identifies Gal-9/Tim-3 as a viable target against PTEN-null glioblastoma Ni, Xiangrong Wu, Weichi Sun, Xiaoqiang Ma, Junxiao Yu, Zhihui He, Xinwei Cheng, Jinyu Xu, Pengfei Liu, Haoxian Shang, Tengze Xi, Shaoyan Wang, Jing Zhang, Ji Chen, Zhongping Sci Adv Biomedicine and Life Sciences Genomic alteration can reshape tumor microenvironment to drive tumor malignancy. However, how PTEN deficiency influences microenvironment-mediated cell-cell interactions in glioblastoma (GBM) remains unclear. Here, we show that PTEN deficiency induces a symbiotic glioma-M2 macrophage interaction to support glioma progression. Mechanistically, PTEN-deficient GBM cells secrete high levels of galectin-9 (Gal-9) via the AKT-GSK3β-IRF1 pathway. The secreted Gal-9 drives macrophage M2 polarization by activating its receptor Tim-3 and downstream pathways in macrophages. These macrophages, in turn, secrete VEGFA to stimulate angiogenesis and support glioma growth. Furthermore, enhanced Gal-9/Tim-3 expression predicts poor outcome in glioma patients. In GBM models, blockade of Gal-9/Tim-3 signaling inhibits macrophage M2 polarization and suppresses tumor growth. Moreover, α-lactose attenuates glioma angiogenesis by down-regulating macrophage-derived VEGFA, providing a novel antivascularization strategy. Therefore, our study suggests that blockade of Gal-9/Tim-3 signaling is effective to impair glioma progression by inhibiting macrophage M2 polarization, specifically for PTEN-null GBM. American Association for the Advancement of Science 2022-07-08 /pmc/articles/PMC9269888/ /pubmed/35857445 http://dx.doi.org/10.1126/sciadv.abl5165 Text en Copyright © 2022 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). https://creativecommons.org/licenses/by-nc/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license (https://creativecommons.org/licenses/by-nc/4.0/) , which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited. |
spellingShingle | Biomedicine and Life Sciences Ni, Xiangrong Wu, Weichi Sun, Xiaoqiang Ma, Junxiao Yu, Zhihui He, Xinwei Cheng, Jinyu Xu, Pengfei Liu, Haoxian Shang, Tengze Xi, Shaoyan Wang, Jing Zhang, Ji Chen, Zhongping Interrogating glioma-M2 macrophage interactions identifies Gal-9/Tim-3 as a viable target against PTEN-null glioblastoma |
title | Interrogating glioma-M2 macrophage interactions identifies Gal-9/Tim-3 as a viable target against PTEN-null glioblastoma |
title_full | Interrogating glioma-M2 macrophage interactions identifies Gal-9/Tim-3 as a viable target against PTEN-null glioblastoma |
title_fullStr | Interrogating glioma-M2 macrophage interactions identifies Gal-9/Tim-3 as a viable target against PTEN-null glioblastoma |
title_full_unstemmed | Interrogating glioma-M2 macrophage interactions identifies Gal-9/Tim-3 as a viable target against PTEN-null glioblastoma |
title_short | Interrogating glioma-M2 macrophage interactions identifies Gal-9/Tim-3 as a viable target against PTEN-null glioblastoma |
title_sort | interrogating glioma-m2 macrophage interactions identifies gal-9/tim-3 as a viable target against pten-null glioblastoma |
topic | Biomedicine and Life Sciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9269888/ https://www.ncbi.nlm.nih.gov/pubmed/35857445 http://dx.doi.org/10.1126/sciadv.abl5165 |
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