Cancer stem cells (CSCs) are a neoplastic subpopulation within solid tumors that are capable of self-renewal and driving tumor propagation. CSCs have been demonstrated to play critical roles in therapeutic resistance, tumor angiogenesis, invasion, and metastasis. Regions of restricted oxygen in solid tumors have also been implicated in radiation resistance and are a negative prognostic indicator for patient survival. It is theorized that the CSC population may reside in microenvironmental niches created by restricted oxygen levels and this drives aggressive tumor behavior. In order to improve patient outcome, it is important to understand the role of oxygen tension in the tumor microenvironment as it pertains to the CSC subpopulation. Our lab previously examined the role of oxygen response factors, the hypoxia inducible factors (HIFs), in CSCs.My thesis work investigates the role of HIF2-alpha in CSCs and how it may be responsible for promoting the CSC phenotype and enhancing the tumorigenic potential of the non-stem population.
Lathia J, Gallagher J, Heddleston JM, Wang J, Eyler CE, MacSwords J, Wu Q, Vasanji A, McLendon RE, Hjelmeland AB, Rich JN. Integrin alpha 6 regulates glioblastoma stem cells. Cell Stem Cell 2010 [In Press]
Hjelmeland AB, Wu Q, Wickman S, Eyler C, Heddleston JM, Shi Q, Lathia JD, Macswords J, Lee J, McLendon RE, Rich JN.Targeting A20 decreases glioma stem cell survival and tumor growth. PLoS Biol. 2010 Feb 23;8(2):e1000319. [PubMed]
Heddleston JM, Li Z, Lathia JD, Bao S, Hjelmeland AB, Rich JN. Hypoxia inducible factors in cancer stem cells.Br J Cancer. 2010 Mar 2;102(5):789-95. Epub 2010 Jan 26. Review. [PubMed]
Heddleston JM, Li Z, McLendon RE, Hjelmeland AB, Rich JN.;The hypoxic microenvironment maintains glioblastoma stem cells and promotes reprogramming towards a cancer stem cell phenotype. Cell Cycle. 2009 Oct 15;8(20):3274-84. Epub 2009 Oct 3. [PubMed]
Wang H, Lathia JD, Wu Q, Wang J, Li Z, Heddleston JM, Eyler CE, Elderbroom J, Gallagher J, Schuschu J, MacSwords J, Cao Y, McLendon RE, Wang XF, Hjelmeland AB, Rich JN.; Targeting interleukin 6 signaling suppresses glioma stem cell survival and tumor growth. Stem Cells. 2009 Oct;27(10):2393-404. [PubMed]