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PMID: 21907924 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Asymmetry-defective oligodendrocyte progenitors are glioma precursors.

Cancer cell ·Vol. 20 ·No. 3 ·2011-09-13 ·Pages 328-40

Sugiarto S, Persson AI, Munoz EG, Waldhuber M, Lamagna C, Andor N, Hanecker P, Ayers-Ringler J, Phillips J, Siu J, Lim DA, Vandenberg S, Stallcup W, Berger MS, Bergers G, Weiss WA, Petritsch C

Abstract

Postnatal oligodendrocyte progenitor cells (OPC) self-renew, generate mature oligodendrocytes, and are a cellular origin of oligodendrogliomas. We show that the proteoglycan NG2 segregates asymmetrically during mitosis to generate OPC cells of distinct fate. NG2 is required for asymmetric segregation of EGFR to the NG2(+) progeny, which consequently activates EGFR and undergoes EGF-dependent proliferation and self-renewal. In contrast, the NG2(-) progeny differentiates. In a mouse model, decreased NG2 asymmetry coincides with premalignant, abnormal self-renewal rather than differentiation and with tumor-initiating potential. Asymmetric division of human NG2(+) cells is prevalent in non-neoplastic tissue but is decreased in oligodendrogliomas. Regulators of asymmetric cell division are misexpressed in low-grade oligodendrogliomas. Our results identify loss of asymmetric division associated with the neoplastic transformation of OPC.

MeSH Terms
Animals Antigens/genetics,metabolism Brain Cell Differentiation Cell Division Cell Proliferation Cell Transformation, Neoplastic Cells, Cultured ErbB Receptors/genetics,metabolism Glioma/genetics,metabolism,pathology Humans Mice Mice, Transgenic Mutation Oligodendroglia/cytology,metabolism,physiology Oligodendroglioma/pathology Proteoglycans/deficiency,genetics,metabolism Stem Cells/cytology,metabolism,physiology
Chemicals
Antigens Proteoglycans chondroitin sulfate proteoglycan 4 ErbB Receptors
Authors & Affiliations
17 authors, click to expand affiliations / ORCID
Sugiarto Sista
Department of Neurological Surgery, University of California San Francisco, USA.
Persson Anders I
Munoz Elena Gonzalez
Waldhuber Markus
Lamagna Chrystelle
Andor Noemi
Hanecker Patrizia
Ayers-Ringler Jennifer
Phillips Joanna
Siu Jason
Lim Daniel A
Vandenberg Scott
Stallcup William
Berger Mitchel S
Bergers Gabriele
Weiss William A
Petritsch Claudia
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Article Info
Journal
Cancer cell
Abbr.
Cancer Cell
ISSN
1878-3686
DOI
10.1016/j.ccr.2011.08.011
Published
2011-09-13
Pages
328-40
Language
English
Region
United States
NLM ID
101130617
PMCID
PMC3297490
Subset
IM
Grants
PHS HHS · R01 164746 · United States
NCI NIH HHS · R01 CA095287 · United States
NCI NIH HHS · R01 CA164746 · United States
NCI NIH HHS · P50 CA097257 · United States
NCI NIH HHS · R01 CA164746-01 · United States
External Links
PubMed source DOI: 10.1016/j.ccr.2011.08.011 PMC Full Text View journal details
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