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Review
. 2021 Jan 1;11(2):665-683.
doi: 10.7150/thno.41692. eCollection 2021.

Glioma stem cells and their roles within the hypoxic tumor microenvironment

Nathaniel H Boyd  1 , Anh Nhat Tran  2 , Joshua D Bernstock  3 , Tina Etminan  4 , Amber B Jones  1 , G Yancey Gillespie  5 , Gregory K Friedman  6 , Anita B Hjelmeland  1   5
Affiliations
Review

Glioma stem cells and their roles within the hypoxic tumor microenvironment

Nathaniel H Boyd et al. Theranostics. .

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; cancer stem cells; glioma; hypoxia; tumor microenvironment.

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Conflict of interest statement

Competing Interests: Dr. Bernstock has positions/equity in CITC Ltd and Avidea Technologies and is member of the POCKiT Diagnostics Board of Scientific Advisors. Dr. Gillespie has positions/equity in Treovir, LLC and Aettis, Inc. The remaining authors declare that they have no conflict(s) of interest.

Figures

Figure 1
Figure 1
Hypoxia and acidic stress exist in microenvironmental niches for brain tumor initiating cells. Normally represented together as necrotic zones, they are also found separately in brain tumors and can independently affect biologies and gene expression patterns.
Figure 2
Figure 2
Hypoxia response genes in glioma and their subsequent downstream biologies relevant to BTICs in Li et al. 2009 and Keith et al. 2011.
Figure 3
Figure 3
Carbonic anhydrase 9 functions to modulate extracellular and intracellular pH by generating protons and bicarbonate via hydrolysis of carbon dioxide and water. This enzyme works in tandem with sodium bicarbonate transporters that import bicarbonate into the cell to buffer intracellular pH.
Figure 4
Figure 4
Hypoxia or HIF-based diagnostics and therapeutics currently in clinical trial for gliomas. Numbers in each section correspond to studies listed as current on clinicaltrials.gov.
See this image and copyright information in PMC

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