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PDPN marks a subset of aggressive and radiation-resistant glioblastoma cells
Treatment-resistant glioma stem cells are thought to propagate and drive growth of malignant gliomas, but their markers and our ability to target them specifically are not well understood. We demonstrate that podoplanin (PDPN) expression is an independent prognostic marker in gliomas across multiple...
| Autores principales: | , , , , , , , , , , , , , , , , , |
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
Frontiers Media S.A.
2022
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| Materias: | |
| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9434399/ https://www.ncbi.nlm.nih.gov/pubmed/36059614 http://dx.doi.org/10.3389/fonc.2022.941657 |
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| author | Modrek, Aram S. Eskilsson, Eskil Ezhilarasan, Ravesanker Wang, Qianghu Goodman, Lindsey D. Ding, Yingwen Zhang, Ze-Yan Bhat, Krishna P. L. Le, Thanh-Thuy T. Barthel, Floris P. Tang, Ming Yang, Jie Long, Lihong Gumin, Joy Lang, Frederick F. Verhaak, Roel G. W. Aldape, Kenneth D. Sulman, Erik P. |
| author_facet | Modrek, Aram S. Eskilsson, Eskil Ezhilarasan, Ravesanker Wang, Qianghu Goodman, Lindsey D. Ding, Yingwen Zhang, Ze-Yan Bhat, Krishna P. L. Le, Thanh-Thuy T. Barthel, Floris P. Tang, Ming Yang, Jie Long, Lihong Gumin, Joy Lang, Frederick F. Verhaak, Roel G. W. Aldape, Kenneth D. Sulman, Erik P. |
| author_sort | Modrek, Aram S. |
| collection | PubMed |
| description | Treatment-resistant glioma stem cells are thought to propagate and drive growth of malignant gliomas, but their markers and our ability to target them specifically are not well understood. We demonstrate that podoplanin (PDPN) expression is an independent prognostic marker in gliomas across multiple independent patient cohorts comprising both high- and low-grade gliomas. Knockdown of PDPN radiosensitized glioma cell lines and glioma-stem-like cells (GSCs). Clonogenic assays and xenograft experiments revealed that PDPN expression was associated with radiotherapy resistance and tumor aggressiveness. We further demonstrate that knockdown of PDPN in GSCs in vivo is sufficient to improve overall survival in an intracranial xenograft mouse model. PDPN therefore identifies a subset of aggressive, treatment-resistant glioma cells responsible for radiation resistance and may serve as a novel therapeutic target. |
| format | Online Article Text |
| id | pubmed-9434399 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2022 |
| publisher | Frontiers Media S.A. |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-94343992022-09-02 PDPN marks a subset of aggressive and radiation-resistant glioblastoma cells Modrek, Aram S. Eskilsson, Eskil Ezhilarasan, Ravesanker Wang, Qianghu Goodman, Lindsey D. Ding, Yingwen Zhang, Ze-Yan Bhat, Krishna P. L. Le, Thanh-Thuy T. Barthel, Floris P. Tang, Ming Yang, Jie Long, Lihong Gumin, Joy Lang, Frederick F. Verhaak, Roel G. W. Aldape, Kenneth D. Sulman, Erik P. Front Oncol Oncology Treatment-resistant glioma stem cells are thought to propagate and drive growth of malignant gliomas, but their markers and our ability to target them specifically are not well understood. We demonstrate that podoplanin (PDPN) expression is an independent prognostic marker in gliomas across multiple independent patient cohorts comprising both high- and low-grade gliomas. Knockdown of PDPN radiosensitized glioma cell lines and glioma-stem-like cells (GSCs). Clonogenic assays and xenograft experiments revealed that PDPN expression was associated with radiotherapy resistance and tumor aggressiveness. We further demonstrate that knockdown of PDPN in GSCs in vivo is sufficient to improve overall survival in an intracranial xenograft mouse model. PDPN therefore identifies a subset of aggressive, treatment-resistant glioma cells responsible for radiation resistance and may serve as a novel therapeutic target. Frontiers Media S.A. 2022-08-10 /pmc/articles/PMC9434399/ /pubmed/36059614 http://dx.doi.org/10.3389/fonc.2022.941657 Text en Copyright © 2022 Modrek, Eskilsson, Ezhilarasan, Wang, Goodman, Ding, Zhang, Bhat, Le, Barthel, Tang, Yang, Long, Gumin, Lang, Verhaak, Aldape and Sulman https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
| spellingShingle | Oncology Modrek, Aram S. Eskilsson, Eskil Ezhilarasan, Ravesanker Wang, Qianghu Goodman, Lindsey D. Ding, Yingwen Zhang, Ze-Yan Bhat, Krishna P. L. Le, Thanh-Thuy T. Barthel, Floris P. Tang, Ming Yang, Jie Long, Lihong Gumin, Joy Lang, Frederick F. Verhaak, Roel G. W. Aldape, Kenneth D. Sulman, Erik P. PDPN marks a subset of aggressive and radiation-resistant glioblastoma cells |
| title | PDPN marks a subset of aggressive and radiation-resistant glioblastoma cells |
| title_full | PDPN marks a subset of aggressive and radiation-resistant glioblastoma cells |
| title_fullStr | PDPN marks a subset of aggressive and radiation-resistant glioblastoma cells |
| title_full_unstemmed | PDPN marks a subset of aggressive and radiation-resistant glioblastoma cells |
| title_short | PDPN marks a subset of aggressive and radiation-resistant glioblastoma cells |
| title_sort | pdpn marks a subset of aggressive and radiation-resistant glioblastoma cells |
| topic | Oncology |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9434399/ https://www.ncbi.nlm.nih.gov/pubmed/36059614 http://dx.doi.org/10.3389/fonc.2022.941657 |
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