Acidic stress promotes a glioma stem cell phenotype.
Published
Journal Article
Malignant gliomas are lethal cancers that display cellular hierarchies with cancer stem cells at the apex. Glioma stem cells (GSCs) are not uniformly distributed, but rather located in specialized niches, suggesting that the cancer stem cell phenotype is regulated by the tumor microenvironment. Indeed, recent studies show that hypoxia and its molecular responses regulate cancer stem cell maintenance. We now demonstrate that acidic conditions, independent of restricted oxygen, promote the expression of GSC markers, self-renewal and tumor growth. GSCs exert paracrine effects on tumor growth through elaboration of angiogenic factors, and low pH conditions augment this expression associated with induction of hypoxia inducible factor 2α (HIF2α), a GSC-specific regulator. Induction of HIF2α and other GSC markers by acidic stress can be reverted by elevating pH in vitro, suggesting that raising intratumoral pH may be beneficial for targeting the GSC phenotype. Together, our results suggest that exposure to low pH promotes malignancy through the induction of a cancer stem cell phenotype, and that culturing cancer cells at lower pH reflective of endogenous tumor conditions may better retain the cellular heterogeneity found in tumors.
Full Text
Duke Authors
Cited Authors
- Hjelmeland, AB; Wu, Q; Heddleston, JM; Choudhary, GS; MacSwords, J; Lathia, JD; McLendon, R; Lindner, D; Sloan, A; Rich, JN
Published Date
- May 2011
Published In
Volume / Issue
- 18 / 5
Start / End Page
- 829 - 840
PubMed ID
- 21127501
Pubmed Central ID
- 21127501
Electronic International Standard Serial Number (EISSN)
- 1476-5403
Digital Object Identifier (DOI)
- 10.1038/cdd.2010.150
Language
- eng
Conference Location
- England