Document Type
Article
Publication Date
1-1-2022
Publication Title
Frontiers in oncology
Keywords
JGM, CD133, PDPN, glioblastoma, glioma, neuro-oncology, podoplanin, radiation oncology, radioresistance
JAX Source
Front Oncol . 2022 Aug 10:12:941657.
Volume
12
First Page
941657
ISSN
2234-943X
PMID
36059614
DOI
10.3389/fonc.2022.941657
Grant
This work was supported by the NIH/NCI under award numbers R01CA190121 (ES, RV), P50CA127001 (ES, RV, KA, FL), P01CA085878 (RV), and P30CA016672 Cancer Center Support Grant (flow cytometry and cellular imaging, the research animal support, and sequencing and microarray facilities); by the American Brain Tumor Association (ES); by the National Brain Tumor Society Defeat GBM Research Collaborative (ES, RV, FL); by the Cancer Prevention and Research Institute of Texas under award number RP120256 (ES, FL, RV) and RP140606 (RV); and by the Broach Foundation (FL)
Abstract
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.
Recommended Citation
Modrek AS,
Eskilsson E,
Ezhilarasan R,
Wang Q,
Goodman LD,
Ding Y,
Zhang Z,
Bhat KP,
Le TT,
Barthel F,
Tang M,
Yang J,
Long L,
Gumin J,
Lang FF,
Verhaak R,
Aldape KD,
Sulman EP.
PDPN marks a subset of aggressive and radiation-resistant glioblastoma cells Front Oncol . 2022 Aug 10:12:941657.
Comments
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