期刊
MACROMOLECULAR BIOSCIENCE
卷 17, 期 8, 页码 -出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/mabi.201700018
关键词
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资金
- Illini 4000
- Mayo Clinic University of Illinois Alliance for Technology-Based Healthcare
- NIH [R01 CA197488, T32 EB019944]
- Department of Chemical & Biomolecular Engineering at the University of Illinois at Urbana-Champaign
- Carl R. Woese Institute for Genomic Biology at the University of Illinois at Urbana-Champaign
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.
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