Mouse Models of Pediatric Supratentorial High-grade Glioma Reveal How Cell-of-Origin Influences Tumor Development and Phenotype.
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Sreedharan S, Maturi NP, Xie Y, Sundström A, Jarvius M, Libard S, Alafuzoff I, Weishaupt H, Fryknäs M, Larsson R, Swartling FJ, Uhrbom L
Cancer Res. 77 (3) 802-812 [2017-02-01; online 2016-11-15]
High-grade glioma (HGG) is a group of primary malignant brain tumors with dismal prognosis. Whereas adult HGG has been studied extensively, childhood HGG, a relatively rare disease, is less well-characterized. Here, we present two novel platelet-derived growth factor (PDGF)-driven mouse models of pediatric supratentorial HGG. Tumors developed from two different cells of origin reminiscent of neural stem cells (NSC) or oligodendrocyte precursor cells (OPC). Cross-species transcriptomics showed that both models are closely related to human pediatric HGG as compared with adult HGG. Furthermore, an NSC-like cell-of-origin enhanced tumor incidence, malignancy, and the ability of mouse glioma cells (GC) to be cultured under stem cell conditions as compared with an OPC-like cell. Functional analyses of cultured GC from these tumors showed that cells of NSC-like origin were more tumorigenic, had a higher rate of self-renewal and proliferation, and were more sensitive to a panel of cancer drugs compared with GC of a more differentiated origin. These two mouse models relevant to human pediatric supratentorial HGG propose an important role of the cell-of-origin for clinicopathologic features of this disease. Cancer Res; 77(3); 802-12. ©2016 AACR.
PubMed 28115362
DOI 10.1158/0008-5472.CAN-16-2482
Crossref 10.1158/0008-5472.CAN-16-2482
pii: 0008-5472.CAN-16-2482