Extracellular Hyaluronic Acid Influences the Efficacy of EGFR Tyrosine Kinase Inhibitors in a Biomaterial Model of Glioblastoma.
Extracellular Hyaluronic Acid Influences the Efficacy of EGFR Tyrosine Kinase Inhibitors in a Biomaterial Model of Glioblastoma.
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DOI：
10.1002/adhm.201700529
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发表时间：
2017-11
影响因子：
10
通讯作者：
Harley BAC
中科院分区：
文献类型：
--
作者：
Pedron S;Hanselman JS;Schroeder MA;Sarkaria JN;Harley BAC
3D biomaterial models have potential to explore the influence of the tumor microenvironment on aberrant signaling pathways and compensatory signals using patient-derived cells. Glioblastoma (GBM) tumors are highly heterogeneous, with both cell composition and extracellular matrix biophysical factors seen as key regulators of malignant phenotype and treatment outcomes. Amplification, overexpression, and mutation of the epidermal growth factor receptor (EGFR) tyrosine kinase have been identified in 50% of GBM patients. Here, hyaluronic acid (HA) decorated methacrylamide-functionalized gelatin (GelMA) hydrogels are used to examine the synergies between microenvironmental factors and a model EGFR tyrosine kinase inhibitor (TKI) using patient-derived xenograft cells. The in vitro behavior of 3 patient-derived xenografts that reflect a clinically relevant range of EGFR variants is characterized: GBM10 (EGFR, wild type), GBM12 (EGFR+), and GBM6 (EGFRvIII). GelMA hydrogels support xenograft culture; cells remain viable, active, respond to matrix-immobilized HA, and upregulate genes associated with matrix remodeling and tumor growth. Interestingly, matrix-immobilized HA alters the response of GBM cells to a model tyrosine kinase inhibitor, erlotinib. While constitutively activated EGFRvIII cells are sensitive to TKI in gelatin hydrogels, hyaluronic acid mediated adhesive signaling interacts with EGFRvIII signaling to increase cell metabolic activity, increase soluble hyaluronic acid synthesis, and modify response to erlotinib exposure.
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DOI：
10.1158/1541-7786.mcr-13-0629
发表时间：
2014-10
期刊：
Molecular cancer research : MCR
影响因子：
--
作者：
Kim Y;Kumar S
通讯作者：
Kumar S
影响因子：
4.6
作者：
Cha J;Kang SG;Kim P
通讯作者：
Kim P
影响因子：
3.7
作者：
Cerami E;Demir E;Schultz N;Taylor BS;Sander C
通讯作者：
Sander C
影响因子：
14
作者：
Ananthanarayanan, Badriprasad;Kim, Yushan;Kumar, Sanjay
通讯作者：
Kumar, Sanjay
影响因子：
7
作者：
Johnson, Hannah;Del Rosario, Amanda M.;White, Forest M.
通讯作者：
White, Forest M.