title: Hemangioblastomas share protein expression with embryonal hemangioblast progenitor cell.
abstract: 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.
authors.affiliation: Surgical Neurology Branch, National Institutes of Neurological Disorders and Stroke, NIH, Bethesda, Maryland 20892, USA.
authors.forename: Sven
authors.initials: S
authors.lastname: Gläsker
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.forename: John B
authors.initials: JB
authors.lastname: Xia
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Okamoto
authors.forename: Weifen
authors.initials: W
authors.lastname: Zeng
authors.forename: Russell R
authors.initials: RR
authors.lastname: Lonser
authors.forename: Zhengping
authors.initials: Z
authors.lastname: Zhuang
authors.forename: Edward H
authors.initials: EH
authors.lastname: Oldfield
authors.forename: Alexander O
authors.initials: AO
authors.lastname: Vortmeyer
mesh_terms: D042683:Angiopoietin-1 / Q000096:biosynthesis; D051792:Basic Helix-Loop-Helix Proteins / Q000096:biosynthesis; D002528:Cerebellar Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D005326:Fetal Proteins / Q000096:biosynthesis; D050982:GATA1 Transcription Factor / Q000096:biosynthesis; D018325:Hemangioblastoma / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D014176:Protein Biosynthesis; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000096:biosynthesis; D042787:Receptor, TIE-2 / Q000096:biosynthesis; D017154:Stromal Cells / Q000378:metabolism; D020825:T-Box Domain Proteins / Q000096:biosynthesis; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000096:biosynthesis; D000098908:Brachyury Protein
chemical_list: D042683:Angiopoietin-1; D051792:Basic Helix-Loop-Helix Proteins; D005326:Fetal Proteins; D050982:GATA1 Transcription Factor; D011518:Proto-Oncogene Proteins; D016186:Receptor, Macrophage Colony-Stimulating Factor; D042787:Receptor, TIE-2; D020825:T-Box Domain Proteins; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; D040301:Vascular Endothelial Growth Factor Receptor-2; D000098908:Brachyury Protein; C494688:GATA1 protein, human; C067143:TAL1 protein, human