Abstract
Abstract Hypoxia (low oxygen) has been associated with adverse effects in tumor biology by exaggerating the capabilities of invasion, proliferation, and survival of tumor cells within the tumor microenvironment. We engineered glioblastoma (GBM) proneural cells with a novel hypoxia reporter, HRE-UnaG, to study areas of tumor hypoxia and the effects that these hypoxic cells have on tumorigenesis. Single cell RNA-seq analysis from a mouse intracranially injected with our HRE dUnaG GBM cells revealed a shift to a mesenchymal state upon hypoxia (detected by expression of UnaG). Two genes, CXCR4 and NXPH4, were identified as being specifically induced in the hypoxic population. Our studies focus on the hypothesis that these two hypoxia induced genes, CXCR4 and NXPH4, are upregulated in hypoxic GBM cells, which may allow tumor cells to become more aggressive and resistant to conventional forms of therapies. GBM cells will be transduced with lentiviral vectors for Dox inducible shRNA knockdown of CXCR4 or NXPH4 to test specific contribution of these genes to the phenotype of the hypoxic population, with particular focus on the change in invasion and overall tumor burden upon gene silencing.
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