1. ABCG2 regulates self-renewal and stem cell marker expression but not tumorigenicity or radiation resistance of glioma cells.
- Author
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Wee B, Pietras A, Ozawa T, Bazzoli E, Podlaha O, Antczak C, Westermark B, Nelander S, Uhrbom L, Forsberg-Nilsson K, Djaballah H, Michor F, and Holland EC
- Subjects
- Animals, Biomarkers, Tumor metabolism, Brain Neoplasms genetics, Brain Neoplasms metabolism, Brain Neoplasms radiotherapy, Cell Line, Tumor, Gene Expression Regulation, Neoplastic radiation effects, Glioma genetics, Glioma metabolism, Glioma radiotherapy, Humans, Mice, Neoplasm Transplantation, Neoplastic Stem Cells radiation effects, Radiation Tolerance, Receptors, Notch metabolism, Signal Transduction radiation effects, Up-Regulation, ATP Binding Cassette Transporter, Subfamily G, Member 2 metabolism, Biomarkers, Tumor genetics, Brain Neoplasms pathology, Glioma pathology, Neoplasm Proteins metabolism, Neoplastic Stem Cells metabolism
- Abstract
Glioma cells with stem cell traits are thought to be responsible for tumor maintenance and therapeutic failure. Such cells can be enriched based on their inherent drug efflux capability mediated by the ABC transporter ABCG2 using the side population assay, and their characteristics include increased self-renewal, high stem cell marker expression and high tumorigenic capacity in vivo. Here, we show that ABCG2 can actively drive expression of stem cell markers and self-renewal in glioma cells. Stem cell markers and self-renewal was enriched in cells with high ABCG2 activity, and could be specifically inhibited by pharmacological and genetic ABCG2 inhibition. Importantly, despite regulating these key characteristics of stem-like tumor cells, ABCG2 activity did not affect radiation resistance or tumorigenicity in vivo. ABCG2 effects were Notch-independent and mediated by diverse mechanisms including the transcription factor Mef. Our data demonstrate that characteristics of tumor stem cells are separable, and highlight ABCG2 as a potential driver of glioma stemness.
- Published
- 2016
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