Stmc-18. anatomic compartmentalization of cancer stem cell signatures in glioblastoma

Cancer stem cells (CSCs) can be defined by functional attributes that include tumor initiation, persistent proliferation, and sustained self-renewal, but their gene signatures and specific anatomic contexts remain obscure. To characterize candidate signatures and explore specific locations in glioblastoma enriched for putative CSCs, we analyzed 270 transcriptomes of anatomic features and CSC profiles of the Ivy Glioblastoma Atlas (http://glioblastoma.alleninstitute.org/). The features included the leading edge, infiltrating tumor (transition zone between leading edge and cellular tumor), cellular tumor, pseudopalisading cells around necrosis, and microvascular proliferation, while the CSC profiles or clusters of putative CSCs were identified by RNA in situ hybridization analysis with probes to CD44, DANCR, HIF1A, ID1, ID2, IGFBP2, ITGA6, MET, MYC, NOS2, PDGFRA, PDPN, PI3, POSTN, PROM1, TGFBR2, or TNFAIP3. We found that histologically-distinct anatomic features exhibit highly conserved gene expression signatures across tumors despite intratumor and intertumor heterogeneity. These features provided a framework for defining three anatomic compartments enriched for putative CSC profiles on the basis of published CSC and cell type or phenotype signatures: a proliferative cellular tumor compartment, a blood vessel compartment, and a quiescent hypoxic compartment associated with immune cells. Compartmental organization of the CSC profiles is consistent with subtype-selective and ana...
Source: Neuro-Oncology - Category: Cancer & Oncology Authors: Tags: STEM CELLS Source Type: research