Hypoxia in the glioblastoma microenvironment: shaping the phenotype of cancer stem-like cells.
Glioblastoma is the most common and aggressive malignant primary brain tumor. Cellular heterogeneity is a characteristic feature of the disease and contributes to the difficulty in formulating effective therapies. Glioma stem-like cells (GSCs) have been identified as a subpopulation of tumor cells that are thought to be largely responsible for resistance to treatment. Intratumoral hypoxia contributes to maintenance of the GSCs by supporting the critical stem cell traits of multipotency, self-renewal, and tumorigenicity. This review highlights the interaction of GSCs with the hypoxic tumor microenvironment, exploring the mechanisms underlying the contribution of GSCs to tumor vessel dynamics, immune modulation, and metabolic alteration.
Neuro-Oncology Branch, National Cancer Institute and National Institute of Neurological Disorders and Stroke, Bethesda, Maryland ; Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, Bethesda, Maryland.
Nicole
N
Colwell
Neuro-Oncology Branch, National Cancer Institute and National Institute of Neurological Disorders and Stroke, Bethesda, Maryland ; Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, Bethesda, Maryland.
Mioara
M
Larion
Neuro-Oncology Branch, National Cancer Institute and National Institute of Neurological Disorders and Stroke, Bethesda, Maryland ; Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, Bethesda, Maryland.
Amber J
AJ
Giles
Neuro-Oncology Branch, National Cancer Institute and National Institute of Neurological Disorders and Stroke, Bethesda, Maryland ; Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, Bethesda, Maryland.
Ashlee N
AN
Seldomridge
Neuro-Oncology Branch, National Cancer Institute and National Institute of Neurological Disorders and Stroke, Bethesda, Maryland ; Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, Bethesda, Maryland.
Saman
S
Sizdahkhani
Neuro-Oncology Branch, National Cancer Institute and National Institute of Neurological Disorders and Stroke, Bethesda, Maryland ; Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, Bethesda, Maryland.
Mark R
MR
Gilbert
Neuro-Oncology Branch, National Cancer Institute and National Institute of Neurological Disorders and Stroke, Bethesda, Maryland ; Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, Bethesda, Maryland.
Deric M
DM
Park
D000818:Animals; D001932:Brain Neoplasms / Q000150:complications / Q000378:metabolism*; D005909:Glioblastoma / Q000150:complications / Q000378:metabolism*; D006801:Humans; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D009389:Neovascularization, Pathologic / Q000150:complications / Q000378:metabolism; D010641:Phenotype; D000072258:Tumor Hypoxia; D059016:Tumor Microenvironment
cancer stem cell; glioblastoma; hypoxia; tumor metabolism