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Cell, Tumor, and Stem Cell Biology |
1 Surgical Neurology Branch, National Institutes of Neurological Disorders and Stroke, NIH, Bethesda, Maryland and 2 Neurochirurgische Universitätsklinik, Albert-Ludwigs Universität, Freiburg, Germany
Requests for reprints: Alexander Vortmeyer, Surgical Neurology Branch, National Institute of Neurological Diseases and Stroke, Building 10, Room 5D37, 10 Center Drive, Bethesda, MD 20892. Phone: 301-496-5728; Fax: 301-402-0380; E-mail: vortmeyera{at}mail.nih.gov.
Hemangioblastomas are central nervous system (CNS) tumors of unknown histogenesis, which can occur sporadically or in von Hippel-Lindau disease. Hemangioblastomas are composed of neoplastic "stromal" cells of unknown origin, accompanied by intensive reactive angiogenesis. Failure to specify the cytologic origin of the stromal cell has precluded the development of nonsurgical therapies and limits understanding of its basic biology. We report that the stromal cells express proteins (Scl, brachyury, Csf-1R, Gata-1, Flk-1, and Tie-2) that characterize embryonic progenitor cells with hemangioblastic differentiation potential and conclude that embryonic progenitors with hemangioblast potential represent a possible cytologic equivalent of the stromal cell. We also identified a new autocrine/paracrine stimulatory loop between the receptor Tie-2 and the hypoxia-inducible factor target Ang-1, which, combined with previous observations, suggests that a variety of autocrine loops may be initiated in hemangioblastomas, depending on the differentiation status of the tumor cells and the extent of HIF downstream activation. Finally, the consistent identification of Scl in the stromal cells may help explain the unique and characteristic topographical distribution of hemangioblastomas within the CNS. (Cancer Res 2006; 66(8):4167-72)
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