title: The Combined Influence of Hydrogel Stiffness and Matrix-Bound Hyaluronic Acid Content on Glioblastoma Invasion.
abstract: 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.
authors.affiliation: Department of Chemical and Biomolecular Engineering, University of Illinois at Urbana-Champaign, 600 S. Mathews St., Urbana, IL, 61801, USA.
authors.forename: Jee-Wei Emily
authors.initials: JE
authors.lastname: Chen
authors.affiliation: Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, 1206 W. Gregory Dr., Urbana, IL, 61801, USA.
authors.forename: Sara
authors.initials: S
authors.lastname: Pedron
authors.affiliation: Department of Chemical and Biomolecular Engineering, and Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, 600 S. Mathews St., Urbana, IL, 61801, USA.
authors.forename: Brendan A C
authors.initials: BAC
authors.lastname: Harley
mesh_terms: D045744:Cell Line, Tumor; D005909:Glioblastoma / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism*; D006820:Hyaluronic Acid / Q000096:biosynthesis*; D020100:Hydrogels / Q000737:chemistry*; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000378:metabolism*
chemical_list: C497483:CD44 protein, human; D018960:Hyaluronan Receptors; D020100:Hydrogels; D009363:Neoplasm Proteins; D006820:Hyaluronic Acid
keywords: bioengineering; glioblastoma; hydrogel; invasion; stiffness