American Association for Cancer Research
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Supplementary Figure 4 from Mouse Models of Pediatric Supratentorial High-grade Glioma Reveal How Cell-of-Origin Influences Tumor Development and Phenotype

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posted on 2023-03-31, 01:02 authored by Smitha Sreedharan, Naga Prathyusha Maturi, Yuan Xie, Anders Sundström, Malin Jarvius, Sylwia Libard, Irina Alafuzoff, Holger Weishaupt, Mårten Fryknäs, Rolf Larsson, Fredrik J. Swartling, Lene Uhrbom

Figure S4, related to Figure 4. Characterization of mouse neural stem cell cultures CCG/tv-a and CCC/tv-a.

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Swedish Cancer Society

Swedish Childhood Cancer Foundation

Swedish Research Council

Swedish Society for Medical Research

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ARTICLE ABSTRACT

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.

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