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

Wee, Boyoung (author)
Canc Biol & Genet Program, New York, NY 10021 USA.;Brain Tumor Ctr, New York, NY 10021 USA.
Pietras, Alexander (author)
Lund University,Lunds universitet,Avdelningen för translationell cancerforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Hjärntumörers biologi,Forskargrupper vid Lunds universitet,Division of Translational Cancer Research,Department of Laboratory Medicine,Faculty of Medicine,Brain Tumor Biology,Lund University Research Groups,Fred Hutchinson Cancer Research Center,University of Washington, Seattle,Fred Hutchinson Canc Res Ctr, Human Biol Div, Solid Tumor & Translat Res, Seattle, WA 98109 USA.;Univ Washington, Neurosurg & Alvord Brain Tumor Ctr, Seattle, WA 98104 USA.;Lund Univ, Dept Lab Med, Translat Canc Res, SE-22363 Lund, Sweden.
Ozawa, Tatsuya (author)
Fred Hutchinson Canc Res Ctr, Human Biol Div, Solid Tumor & Translat Res, Seattle, WA 98109 USA.;Univ Washington, Neurosurg & Alvord Brain Tumor Ctr, Seattle, WA 98104 USA.,Fred Hutchinson Cancer Research Center
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Bazzoli, Elena (author)
IRCCS, Ctr San Giovanni Di Dio Fatebenefratelli, I-25123 Bs, Italy.,Centro San Giovanni di Dio Fatebenefratelli
Podlaha, Ondrej (author)
Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA.;Harvard Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA.,Dana-Farber Cancer Institute
Antczak, Christophe (author)
Mem Sloan Kettering Canc Ctr, HTS Core Facil, New York, NY 10021 USA.;Novartis Inst Biomed Res, Ctr Prote Chem, 250 Massachusetts Ave, Cambridge, MA 02139 USA.,Memorial Sloan-Kettering Cancer Center
Westermark, Bengt (author)
Uppsala University,Uppsala universitet,Neuroonkologi,Science for Life Laboratory, SciLifeLab
Nelander, Sven (author)
Uppsala University,Uppsala universitet,Neuroonkologi,Science for Life Laboratory, SciLifeLab
Uhrbom, Lene (author)
Uppsala University,Uppsala universitet,Neuroonkologi,Science for Life Laboratory, SciLifeLab
Forsberg-Nilsson, Karin (author)
Uppsala University,Uppsala universitet,Neuroonkologi,Science for Life Laboratory, SciLifeLab
Djaballah, Hakim (author)
Mem Sloan Kettering Canc Ctr, HTS Core Facil, New York, NY 10021 USA.,Memorial Sloan-Kettering Cancer Center
Michor, Franziska (author)
Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA.;Harvard Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA.,Harvard University
Holland, Eric C. (author)
Fred Hutchinson Canc Res Ctr, Human Biol Div, Solid Tumor & Translat Res, Seattle, WA 98109 USA.;Univ Washington, Neurosurg & Alvord Brain Tumor Ctr, Seattle, WA 98104 USA.,University of Washington, Seattle
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Canc Biol & Genet Program, New York, NY 10021 USA;Brain Tumor Ctr, New York, NY 10021 USA. Avdelningen för translationell cancerforskning (creator_code:org_t)
2016-07-26
2016
English.
In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
  • Journal article (peer-reviewed)
Abstract Subject headings
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  • 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.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Neurologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Neurology (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)

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