Winship, Duke journal, GBM's...... QUICK SEARCH: [advanced]Author:Keyword(s):Year: Vol: Page: Home | Help | Feedback | Subscriptions | Archive | Search | Table of ContentsNeuro-oncol 2005 7(2):134-153; DOI:10.1215/S1152851704001115 This ArticleFull Text (PDF) References Alert me when this article is cited Alert me if a correction is posted Citation Map ServicesSimilar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Cited by other online articles Search for citing articles in: ISI Web of Science (2) Google ScholarArticles by Kaur, B. Articles by Van Meir, E. G. Articles citing this Article PubMedPubMed Citation Duke University Press Tumor BiologyHypoxia and the hypoxia-inducible-factor pathway in glioma growth and angiogenesis Balveen Kaur, Fatima W. Khwaja, Eric A. Severson, Shannon L. Matheny, Daniel J. Brat and Erwin G. Van Meir2 Laboratory of Molecular Neuro-Oncology, Department of Neurosurgery and Hematology/Oncology (F.W.K., E.A.S., S.L.M), and Pathology (D.J.B.), Winship Cancer Institute (B.K., E.G.V.M.), Emory University School of Medicine, Atlanta, GA 30322, USA 2 Address correspondence to Erwin G. Van Meir, Winship Cancer Institute, Emory University School of Medicine, 1365C Clifton Road, NE, Room C5078, Atlanta, GA 30322, USA (evanmei{at}emory.edu).AbstractGlioblastomas, like other solid tumors, have extensive areas of hypoxia and necrosis. The importance of hypoxia in driving tumor growth is receiving increased attention. Hypoxia-inducible factor 1 (HIF-1) is one of the master regulators that orchestrate the cellular responses to hypoxia. It is a heterodimeric transcription factor composed of and ß subunits. The subunit is stable in hypoxic conditions but is rapidly degraded in normoxia. The function of HIF-1 is also modulated by several molecular mechanisms that regulate its synthesis, degradation, and transcriptional activity. Upon stabilization or activation, HIF-1 translocates to the nucleus and induces transcription of its downstream target genes. Most important to gliomagenesis, HIF-1 is a potent activator of angiogenesis and invasion through its upregulation of target genes critical for these functions. Activation of the HIF-1 pathway is a common feature of gliomas and may explain the intense vascular hyperplasia often seen in glioblastoma multiforme. Activation of HIF results in the activation of vascular endothelial growth factors, vascular endothelial growth factor receptors, matrix metalloproteinases, plasminogen activator inhibitor, transforming growth factors and ß, angiopoietin and Tie receptors, endothelin-1, inducible nitric oxide synthase, adrenomedullin, and erythropoietin, which all affect glioma angiogenesis. In conclusion, HIF is a critical regulatory factor in the tumor microenvironment because of its central role in promoting proangiogenic and invasive properties. While HIF activation strongly promotes angiogenesis, the emerging vasculature is often abnormal, leading to a vicious cycle that causes further hypoxia and HIF upregulation. This article has been cited by other articles: (Search Google Scholar for Other Citing Articles) G. Garin, M. Mathews, and B. C. BerkTissue-Resident Bone Marrow-Derived Progenitor Cells: Key Players in Hypoxia-Induced AngiogenesisCirc. Res., November 11, 2005; 97(10): 955 - 957. [Full Text] [PDF] Home | Help | Feedback | Subscriptions | Archive | Search | Table of ContentsCopyright 2005 by Society for Neuro-Oncology
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