The migration and invasion of malignant Glioblastoma (GBM) cells into normal brain parenchyma is fundamentally different than other biological conditions because the biophysical properties of the brain microenvironment are differ from other tissues. These microenvironmental processes contribute to chemotherapy resistance. New microfluidic ex vivo devices, that simulate the microenvironment of tumor cells in the brain, will be used to evaluate the roll of active cell migration through confined spaces in developing treatment resistance by (1) isolating and enriching clonal populations resistant to temozolomide and able to migrate, and (2) testing the roll of candidate genes for chemotherapy resistance. Cell cultures and patient derived stem cell lines will be enriched for migrating and treatment resistance cells to establish clonal populations from heterogeneous cultures. These enrichment techniques will serve as future substrates for treatment resistance models. By preliminary and reported data, ABCG2 is involved in GBM cell migration and treatment resistance. Using the microfluidic channels, the expression pattern and role of ABCG2 will be evaluated for ABCG2 necessity (expression knockdown and inhibitor) and sufficiency (overexpression). We will analyze the expression pattern of ABCG2 to migration, pre-migration, during active migration and post- migration. These results will add to our knowledge of GBM cell migration and establish a platform to test new agents to sensitize migrating cells to conventional treatments.
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