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 gliobla

SUBMITTER: Pietras A 

PROVIDER: S-EPMC3999042 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature