Osteopontin-CD44 signaling in the glioma perivascular niche enhances cancer stem cell phenotypes and promotes aggressive tumor growth Journal Article

   

Authors:	Pietras, A.; Katz, A. M.; Ekstrom, E. J.; Wee, B.; Halliday, J. J.; Pitter, K. L.; Werbeck, J. L.; Amankulor, N. M.; Huse, J. T.; Holland, E. C.
Article Title:	Osteopontin-CD44 signaling in the glioma perivascular niche enhances cancer stem cell phenotypes and promotes aggressive tumor growth
Abstract:	Stem-like glioma cells reside within a perivascular niche and display hallmark radiation resistance. An understanding of the mechanisms underlying these properties will be vital for the development of effective therapies. Here, we show that the stem cell marker CD44 promotes cancer stem cell phenotypes and radiation resistance. In a mouse model of glioma, Cd44-/- and Cd44+/- animals showed improved survival compared to controls. The CD44 ligand osteopontin shared a perivascular expression pattern with CD44 and promoted glioma stem cell-like phenotypes. These effects were mediated via the γ-secretase-regulated intracellular domain of CD44, which promoted aggressive glioma growth in vivo and stem cell-like phenotypes via CBP/p300-dependent enhancement of HIF-2α activity. In human glioblastoma multiforme, expression of CD44 correlated with hypoxia-induced gene signatures and poor survival. Altogether, these data suggest that in the glioma perivascular niche, osteopontin promotes stem cell-like properties and radiation resistance in adjacent tumor cells via activation of CD44 signaling. © 2014 Elsevier Inc.
Keywords:	signal transduction; cancer survival; controlled study; protein expression; human cell; nonhuman; glioma; protein domain; animal cell; mouse; phenotype; gene expression; animal experiment; animal model; in vivo study; correlation analysis; glioblastoma; cancer stem cell; radiosensitivity; tumor growth; molecular biology; hermes antigen; gamma secretase; e1a associated p300 protein; osteopontin; hypoxia inducible factor 2alpha; cyclic amp responsive element binding protein binding protein; human; priority journal; article
Journal Title:	Cell Stem Cell
Volume:	14
Issue:	3
ISSN:	1934-5909
Publisher:	Cell Press
Date Published:	2014-03-06
Start Page:	357
End Page:	369
Language:	English
DOI:	10.1016/j.stem.2014.01.005
PROVIDER:	scopus
PMCID:	PMC3999042
PUBMED:	24607407
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-84896107633&partnerID=40&md5=da6293e92b913a9ceb47d17c39ce1376
Notes:	Cited By (since 1996):1 -- Export Date: 1 August 2014 -- Source: Scopus

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