Glioma stem cells and their roles within the hypoxic tumor microenvironment

Nathaniel H. Boyd¹, Anh Nhat Tran², Joshua D. Bernstock³, Tina Etminan⁴, Amber B. Jones¹, G. Yancey Gillespie⁵, Gregory K. Friedman⁶, Anita B. Hjelmeland^1,5✉

1. Department of Cell, Developmental, and Integrative Biology, University of Alabama at Birmingham, Birmingham, AL.
2. Department of Neurosurgery, Northwestern University, Chicago, IL.
3. Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
4. Department of Chemistry, University of Alabama at Birmingham, Birmingham, AL.
5. Department of Neurosurgery, University of Alabama at Birmingham, Birmingham, AL.
6. Division of Pediatric Hematology and Oncology, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL.

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Citation:
Boyd NH, Tran AN, Bernstock JD, Etminan T, Jones AB, Gillespie GY, Friedman GK, Hjelmeland AB. Glioma stem cells and their roles within the hypoxic tumor microenvironment. Theranostics 2021; 11(2):665-683. doi:10.7150/thno.41692. Available from https://www.thno.org/v11p0665.htm

Abstract

Tumor microenvironments are the result of cellular alterations in cancer that support unrestricted growth and proliferation and result in further modifications in cell behavior, which are critical for tumor progression. Angiogenesis and therapeutic resistance are known to be modulated by hypoxia and other tumor microenvironments, such as acidic stress, both of which are core features of the glioblastoma microenvironment. Hypoxia has also been shown to promote a stem-like state in both non-neoplastic and tumor cells. In glial tumors, glioma stem cells (GSCs) are central in tumor growth, angiogenesis, and therapeutic resistance, and further investigation of the interplay between tumor microenvironments and GSCs is critical to the search for better treatment options for glioblastoma. Accordingly, we summarize the impact of hypoxia and acidic stress on GSC signaling and biologic phenotypes, and potential methods to inhibit these pathways.

Keywords: acidic stress, glioma, hypoxia, cancer stem cells, tumor microenvironment