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

Abstract

Glioblastomais 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 GSC maintenance and 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 slowly‐dividing and 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 and fluorescence microscopy of17 biomarkers in paraffin sections of human glioblastoma and human healthy 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.Support or Funding InformationThis study was financially supported by the Dutch Cancer Society (KWF; UVA 2014‐6839 and UVA 2016.1‐10460), the European Program of Cross‐Border Cooperation for Slovenia‐Italy Interreg TRANS‐GLIOMA (Program 2017), the IVY Interreg Fellowship, the Slovenian Research Agency (Program P10245) and by the Fondation pour la Recherche Nuovo‐Soldati 2019.