Journal
CANCERS
Volume 11, Issue 10, Pages -Publisher
MDPI
DOI: 10.3390/cancers11101564
Keywords
glioblastoma; glioma initiating cell; The Cancer Genome Atlas; molecular classification
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Funding
- JSPS KAKENHI [15K19980]
- Grants-in-Aid for Scientific Research [15K19980] Funding Source: KAKEN
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The Cancer Genome Atlas (TCGA) project described a robust gene expression-based molecular classification of glioblastoma (GBM), but the functional and biological significance of the subclasses has not been determined. The present comprehensive analysis of 25 glioma-initiating cell (GIC) lines classifies GIC lines into four subtypes (classical, mesenchymal, proneural, and neural) that are closely related to the TCGA GBM subclasses and display distinct lineage characteristics and differentiation behavior that recapitulate neural development. More importantly, the GIC subtypes exhibit distinct biological phenotypes in relation to self-renewal capacity, proliferation, invasiveness, and angiogenic potential in vitro and in vivo. In addition, the GIC subtypes exhibit divergent patterns of signaling pathway activation and deactivation of the Wnt, Notch, and TGF-beta pathways. These results will improve drug discovery targeting certain genetic mutation in glioblastoma and improve the development of precision medicine.
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