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

Wee, Boyoung; Pietras, Alexander LU ; Ozawa, Tatsuya; Bazzoli, Elena; Podlaha, Ondrej; Antczak, Christophe; Westermark, Bengt; Nelander, Sven; Uhrbom, Lene and Forsberg-Nilsson, Karin, et al. (2016) In Scientific Reports 6.
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... (More)

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.

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Scientific Reports
volume
6
publisher
Nature Publishing Group
external identifiers
  • scopus:84979626532
  • wos:000380208400001
ISSN
2045-2322
DOI
10.1038/srep25956
language
English
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yes
id
4a0b8aeb-becd-41ac-a4e7-8222c4e01fca
date added to LUP
2016-12-22 12:02:56
date last changed
2017-11-19 04:36:08
@article{4a0b8aeb-becd-41ac-a4e7-8222c4e01fca,
  abstract     = {<p>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.</p>},
  articleno    = {25956},
  author       = {Wee, Boyoung and Pietras, Alexander and Ozawa, Tatsuya and Bazzoli, Elena and Podlaha, Ondrej and Antczak, Christophe and Westermark, Bengt and Nelander, Sven and Uhrbom, Lene and Forsberg-Nilsson, Karin and Djaballah, Hakim and Michor, Franziska and Holland, Eric C.},
  issn         = {2045-2322},
  language     = {eng},
  month        = {07},
  publisher    = {Nature Publishing Group},
  series       = {Scientific Reports},
  title        = {ABCG2 regulates self-renewal and stem cell marker expression but not tumorigenicity or radiation resistance of glioma cells},
  url          = {http://dx.doi.org/10.1038/srep25956},
  volume       = {6},
  year         = {2016},
}