Frontiers in Oncology (Aug 2022)

PDPN marks a subset of aggressive and radiation-resistant glioblastoma cells

  • Aram S. Modrek,
  • Eskil Eskilsson,
  • Ravesanker Ezhilarasan,
  • Qianghu Wang,
  • Lindsey D. Goodman,
  • Yingwen Ding,
  • Ze-Yan Zhang,
  • Krishna P. L. Bhat,
  • Thanh-Thuy T. Le,
  • Floris P. Barthel,
  • Ming Tang,
  • Jie Yang,
  • Lihong Long,
  • Joy Gumin,
  • Frederick F. Lang,
  • Roel G. W. Verhaak,
  • Kenneth D. Aldape,
  • Erik P. Sulman,
  • Erik P. Sulman

DOI
https://doi.org/10.3389/fonc.2022.941657
Journal volume & issue
Vol. 12

Abstract

Read online

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.

Keywords