4.8 Review

Glioma stem cells and their roles within the hypoxic tumor microenvironment

Journal

THERANOSTICS
Volume 11, Issue 2, Pages 665-683

Publisher

IVYSPRING INT PUBL
DOI: 10.7150/thno.41692

Keywords

acidic stress; glioma; hypoxia; cancer stem cells; tumor microenvironment

Funding

  1. National Institutes of Health [R01NS104339, U01CA223976, R21CA252382, F31CA200085]
  2. National Science Foundation
  3. Hyundai Hope on Wheels
  4. Rally Foundation for Childhood Cancer Research
  5. Andrew McDonough B+ Foundation

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Tumor microenvironments result from cellular alterations in cancer that promote unrestricted growth and angiogenesis, with hypoxia and acidic stress known to modulate therapeutic resistance. Understanding the interplay between tumor microenvironments and glioma stem cells is crucial for developing better treatment options for glioblastoma.
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.

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