4.2 Article

Similarities Between Stem Cell Niches in Glioblastoma and Bone Marrow: Rays of Hope for Novel Treatment Strategies

Journal

JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY
Volume 68, Issue 1, Pages 33-57

Publisher

SAGE PUBLICATIONS LTD
DOI: 10.1369/0022155419878416

Keywords

bone marrow; glioblastoma; glioblastoma stem cells; hematopoietic progenitor cells; hematopoietic stem cells; immunohistochemistry; niches

Categories

Funding

  1. Dutch Cancer Society (KWF) [UVA 2014-6839, UVA 2016.1-10460]
  2. European Program of Cross-Border Cooperation for Slovenia-Italy Interreg TRANS-GLIOMA (Program 2017)
  3. IVY Interreg Fellowship
  4. Slovenian Research Agency [P10245]
  5. Fondation pour la Recherche Nuovo-Soldati 2019

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Glioblastoma is the most aggressive primary brain tumor. Slowly dividing and therapy-resistant glioblastoma stem cells (GSCs) reside in protective peri-arteriolar niches and are held responsible for glioblastoma recurrence. Recently, we showed similarities between GSC niches and hematopoietic stem cell (HSC) niches in bone marrow. Acute myeloid leukemia (AML) cells hijack HSC niches and are transformed into therapy-resistant leukemic stem cells (LSCs). Current clinical trials are focussed on removal of LSCs out of HSC niches to differentiate and to become sensitized to chemotherapy. In the present study, we elaborated further on these similarities by immunohistochemical analyses of 17 biomarkers in paraffin sections of human glioblastoma and human bone marrow. We found all 17 biomarkers to be expressed both in hypoxic peri-arteriolar HSC niches in bone marrow and hypoxic peri-arteriolar GSC niches in glioblastoma. Our findings implicate that GSC niches are being formed in glioblastoma as a copy of HSC niches in bone marrow. These similarities between HSC niches and GSC niches provide a theoretic basis for the development of novel strategies to force GSCs out of their niches, in a similar manner as in AML, to induce GSC differentiation and proliferation to render them more sensitive to anti-glioblastoma therapies.

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