Hypoxia-Induced Reactivity of Tumor-Associated Astrocytes Affects Glioma Cell Properties
Division of Translational Cancer Research, Department of Laboratory Medicine, Lund University, 223 63 Lund, Sweden
*
Author to whom correspondence should be addressed.
Academic Editor: Adrian Harris
Cells 2021, 10(3), 613; https://doi.org/10.3390/cells10030613
Received: 19 February 2021
/
Revised: 4 March 2021
/
Accepted: 8 March 2021
/
Published: 10 March 2021
(This article belongs to the Special Issue Hypoxia and Cancer: New Aspects)
Glioblastoma is characterized by extensive necrotic areas with surrounding hypoxia. The cancer cell response to hypoxia in these areas is well-described; it involves a metabolic shift and an increase in stem cell-like characteristics. Less is known about the hypoxic response of tumor-associated astrocytes, a major component of the glioma tumor microenvironment. Here, we used primary human astrocytes and a genetically engineered glioma mouse model to investigate the response of this stromal cell type to hypoxia. We found that astrocytes became reactive in response to intermediate and severe hypoxia, similarly to irradiated and temozolomide-treated astrocytes. Hypoxic astrocytes displayed a potent hypoxia response that appeared to be driven primarily by hypoxia-inducible factor 2-alpha (HIF-2α). This response involved the activation of classical HIF target genes and the increased production of hypoxia-associated cytokines such as TGF-β1, IL-3, angiogenin, VEGF-A, and IL-1 alpha. In vivo, astrocytes were present in proximity to perinecrotic areas surrounding HIF-2α expressing cells, suggesting that hypoxic astrocytes contribute to the glioma microenvironment. Extracellular matrix derived from hypoxic astrocytes increased the proliferation and drug efflux capability of glioma cells. Together, our findings suggest that hypoxic astrocytes are implicated in tumor growth and potentially stemness maintenance by remodeling the tumor microenvironment.
View Full-Text
Keywords:
astrocytes; glioma microenvironment; tumor hypoxia
▼
Show Figures
Figure 1
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited
- Supplementary File 1:
PDF-Document (PDF, 4775 KiB)
MDPI and ACS Style
Pantazopoulou, V.; Jeannot, P.; Rosberg, R.; Berg, T.J.; Pietras, A. Hypoxia-Induced Reactivity of Tumor-Associated Astrocytes Affects Glioma Cell Properties. Cells 2021, 10, 613. https://doi.org/10.3390/cells10030613
AMA Style
Pantazopoulou V, Jeannot P, Rosberg R, Berg TJ, Pietras A. Hypoxia-Induced Reactivity of Tumor-Associated Astrocytes Affects Glioma Cell Properties. Cells. 2021; 10(3):613. https://doi.org/10.3390/cells10030613
Chicago/Turabian StylePantazopoulou, Vasiliki, Pauline Jeannot, Rebecca Rosberg, Tracy J. Berg, and Alexander Pietras. 2021. "Hypoxia-Induced Reactivity of Tumor-Associated Astrocytes Affects Glioma Cell Properties" Cells 10, no. 3: 613. https://doi.org/10.3390/cells10030613
Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.
