Hypoxia activates enhanced invasive potential and endogenous hyaluronic acid production by glioblastoma cells

Biomaterials Science
Jee-Wei Emily ChenBrendan A Harley

Abstract

Glioblastoma (GBM) is the most common, aggressive, and deadly form of adult brain cancer, and is associated with a short survival rate (median 12-15 months, 5+ year less than 5%). The complex tumor microenvironment includes matrix transitions at the tumor margin, such as gradations in hyaluronic acid (HA). In addition, metabolic stress induced by decreased oxygen content across the tumor may contribute to tumor progression. However, cross-talk between matrix composition and metabolic stress remains unclear. In this study, we fabricated an in vitro brain memetic HA-decorated gelatin hydrogel platform incorporating variable oxygen concentrations to mimic intra-tumoral hypoxia. We observed that EGFR status (wildtype vs. a constitutively active EGFRvIII mutant) of U87 GBM cells affected proliferation and metabolic activity in response to hypoxia and matrix-bound HA. The use of an invasion assay revealed that invasion was significantly enhanced in both cell types under hypoxia. Moreover, we observed compensatory secretion of soluble HA in cases of enhanced GBM cell invasion, consistent with our previous findings using other GBM cell lines. Interestingly, U87 GBM cells adapted to hypoxia by shifting toward a more anaerobic metabolic ...Continue Reading

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Citations

Sep 6, 2019·Interface Focus·Samantha G ZambutoBrendan A C Harley
Oct 28, 2019·Frontiers in Oncology·Carlos VelásquezJosé L Fernández-Luna
Aug 31, 2019·Journal of Oncology·Carlos VelásquezJosé L Fernández-Luna
Jun 9, 2020·Integrative Biology : Quantitative Biosciences From Nano to Macro·Mai T NgoBrendan A C Harley
Dec 18, 2020·Frontiers in Cell and Developmental Biology·Anna BarkovskayaValerie M Weaver
Mar 2, 2021·Advanced Science·Barbara Blanco-FernandezJoão F Mano
Mar 22, 2021·The Journal of Biological Chemistry·Matías Arturo PibuelSilvina Laura Lompardía
Apr 20, 2021·APL Bioengineering·Mai T Ngo, Brendan A C Harley
Jul 15, 2021·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Kasra Goodarzi, Shreyas S Rao
Aug 27, 2021·Tissue Engineering. Part a·Jee-Wei Emily ChenBrendan A C Harley

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Methods Mentioned

BETA
electrophoresis
enzyme-linked immunosorbent assay
ELISA

Software Mentioned

Image
ImageJ

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