ABCG2 regulates self-renewal and stem cell marker expression but not tumorigenicity or radiation resistance of glioma cells

Research output: Contribution to journalArticle

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.

Details

Authors
  • Boyoung Wee
  • Alexander Pietras
  • Tatsuya Ozawa
  • Elena Bazzoli
  • Ondrej Podlaha
  • Christophe Antczak
  • Bengt Westermark
  • Sven Nelander
  • Lene Uhrbom
  • Karin Forsberg-Nilsson
  • Hakim Djaballah
  • Franziska Michor
  • Eric C. Holland
Organisations
External organisations
  • Uppsala University
  • Memorial Sloan-Kettering Cancer Center
  • Harvard University
  • University of Washington, Seattle
  • Fred Hutchinson Cancer Research Center
  • Centro San Giovanni di Dio Fatebenefratelli
  • Dana-Farber Cancer Institute
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cell and Molecular Biology
Original languageEnglish
Article number25956
JournalScientific Reports
Volume6
Publication statusPublished - 2016 Jul 26
Publication categoryResearch
Peer-reviewedYes