Differential expression of stem cell markers in proliferating cells in glioma

J Cancer Res Clin Oncol. 2021 Oct;147(10):2969-2982. doi: 10.1007/s00432-021-03704-5. Epub 2021 Jun 25.

Abstract

Purpose: The identification of prognostically and therapeutically relevant molecular markers is fundamental to the further development of personalised therapies in brain tumours. Current therapeutic options for the treatment of gliomas rely mainly on surgical resection and the inhibition of tumour cell proliferation by irradiation and chemotherapy. Glioma stem cells are a subpopulation of proliferating tumour cells that have self-renewal capacity and can give rise to heterogeneous cells that comprise the tumour and are thought to play a role in the resistance of gliomas to therapy. The aim of this study was to evaluate the expression of markers of glioma stem cells and differentiated glial cells in proliferating glioma cells in comparison to the overall expression of the respective markers in the tumour tissue.

Methods: Tissue microarrays were assembled from specimen of pilocytic astrocytoma, diffuse astrocytoma, anaplastic astrocytoma, glioblastoma, oligodendroglioma, anaplastic oligodendroglioma, ependymoma, and anaplastic ependymoma. These were immunohistochemically double stained with antibodies against the proliferation-associated antigen Ki67 and marker proteins for glioma stem cells (CD133, Nestin, Musashi, CD15, CD44), and differentiated glioma cells (GFAP, MAP2c).

Results: The expression of both glial and glioma stem cell markers differs between proliferating and non-proliferating glioma cells. Furthermore, the proliferating cells in the different glial tumour entities show a different expression profile.

Conclusion: Further analysis of marker expression in proliferating glioma cells and correlation with clinical outcome and susceptibility to irradiation and chemotherapy might help establish new biomarkers and therapies for glioma.

Keywords: Expression profile; Glioblastoma; Glioma; Ki67; Proliferating cells; Stem cells.

MeSH terms

  • AC133 Antigen / metabolism
  • Biomarkers, Tumor / metabolism*
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / pathology
  • Cell Proliferation*
  • Gene Expression Regulation, Neoplastic*
  • Glioma / metabolism
  • Glioma / pathology*
  • Humans
  • Hyaluronan Receptors / metabolism
  • Lewis X Antigen / metabolism
  • Neoplastic Stem Cells / metabolism
  • Neoplastic Stem Cells / pathology*
  • Nerve Tissue Proteins / metabolism
  • Nestin / metabolism
  • RNA-Binding Proteins / metabolism

Substances

  • AC133 Antigen
  • Biomarkers, Tumor
  • CD44 protein, human
  • Hyaluronan Receptors
  • Lewis X Antigen
  • MSI1 protein, human
  • NES protein, human
  • Nerve Tissue Proteins
  • Nestin
  • PROM1 protein, human
  • RNA-Binding Proteins