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The Combined Influence of Hydrogel Stiffness and Matrix‐Bound Hyaluronic Acid Content on Glioblastoma Invasion
Author(s) -
Chen JeeWei Emily,
Pedron Sara,
Harley Brendan A. C.
Publication year - 2017
Publication title -
macromolecular bioscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.924
H-Index - 105
eISSN - 1616-5195
pISSN - 1616-5187
DOI - 10.1002/mabi.201700018
Subject(s) - hyaluronic acid , self healing hydrogels , chemistry , dextran , glioblastoma , matrix (chemical analysis) , cd44 , biophysics , in vivo , cancer research , biochemistry , microbiology and biotechnology , in vitro , biology , anatomy , polymer chemistry , chromatography
Glioblastoma (GBM) is the most common and lethal form of brain cancer. Its high mortality is associated with its aggressive invasion throughout the brain. The heterogeneity of stiffness and hyaluronic acid (HA) content within the brain makes it difficult to study invasion in vivo. A dextran‐bead assay is employed to quantify GBM invasion within HA‐functionalized gelatin hydrogels. Using a library of stiffness‐matched hydrogels with variable levels of matrix‐bound HA, it is reported that U251 GBM invasion is enhanced in softer hydrogels but reduced in the presence of matrix‐bound HA. Inhibiting HA–CD44 interactions reduces invasion, even in hydrogels lacking matrix‐bound HA. Analysis of HA biosynthesis suggests that GBM cells compensate for a lack of matrix‐bound HA by producing soluble HA to stimulate invasion. Together, a robust method is showed to quantify GBM invasion over long culture times to reveal the coordinated effect of matrix stiffness, immobilized HA, and compensatory HA production on GBM invasion.