title: Tumor derived vasculogenesis in von Hippel-Lindau disease-associated tumors.
abstract: von Hippel-Lindau disease (VHL) patients develop highly vascular tumors, including central nervous system hemangioblastomas. It has been hypothesized that the vascular nature of these tumors is the product of reactive angiogenesis. However, recent data indicate that VHL-associated hemangioblastoma neoplastic cells originate from embryologically-arrested hemangioblasts capable of blood and endothelial cell differentiation. To determine the origin of tumor vasculature in VHL-associated hemangioblastomas, we analyzed the vascular elements in tumors from VHL patients. We demonstrate that isolated vascular structures and blood vessels within VHL-associated hemangioblastomas are a result of tumor-derived vasculogenesis. Further, similar to hemangioblastomas, we demonstrate that other VHL-associated lesions possess vascular tissue of tumor origin and that tumor-derived endothelial cells emerge within implanted VHL deficient UMRC6 RCC murine xenografts. These findings further establish the embryologic, developmentally arrested, hemangioblast as the tumor cell of origin for VHL-associated hemangioblastomas and indicate that it is also the progenitor cell for other VHL-associated tumors.
authors: 1] Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD [2].
authors: Zhengping
authors: Z
authors: Zhuang
authors: 1] Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD [2].
authors: Jason M
authors: JM
authors: Frerich
authors: Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD.
authors: Kristin
authors: K
authors: Huntoon
authors: Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD.
authors: Chunzhang
authors: C
authors: Yang
authors: Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD.
authors: Marsha J
authors: MJ
authors: Merrill
authors: Laboratory of Pathology, Center for Cancer Research National Cancer Institute, National Institutes of Health, Bethesda, MD.
authors: Ziedulla
authors: Z
authors: Abdullaev
authors: Laboratory of Pathology, Center for Cancer Research National Cancer Institute, National Institutes of Health, Bethesda, MD.
authors: Svetlana D
authors: SD
authors: Pack
authors: Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD.
authors: Sharon B
authors: SB
authors: Shively
authors: Experimental Pathology Laboratory, Cancer Research UK London Research Institute, Fields, London.
authors: Gordon
authors: G
authors: Stamp
authors: 1] Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD [2] Department of Neurological Surgery, The Ohio State University Wexner Medical Center, Department of Neurological Surgery, Columbus, Ohio.
authors: Russell R
authors: RR
authors: Lonser
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002528:Cerebellar Neoplasms / Q000098:blood supply / Q000209:etiology / Q000473:pathology*; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D005169:Factor VIII / Q000378:metabolism; D018325:Hemangioblastoma / Q000098:blood supply / Q000209:etiology / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D019656:Loss of Heterozygosity; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D009389:Neovascularization, Pathologic; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D014183:Transplantation, Heterologous; D006623:von Hippel-Lindau Disease / Q000150:complications / Q000175:diagnosis* / Q000473:pathology
chemical_list: D019408:Platelet Endothelial Cell Adhesion Molecule-1; D005169:Factor VIII