von Hippel-Lindau disease-associated hemangioblastomas are derived from embryologic multipotent cells.

Park, Deric M; Zhuang, Zhengping; Chen, Ling; Szerlip, Nicholas; Maric, Irina; Li, Jie; Sohn, Taesung; Kim, Stephanie H; Lubensky, Irina A; Vortmeyer, Alexander O; Rodgers, Griffin P; Oldfield, Edward H; Lonser, Russell R

Park, Deric M; Zhuang, Zhengping; Chen, Ling; Szerlip, Nicholas; Maric, Irina; Li, Jie; Sohn, Taesung; Kim, Stephanie H; Lubensky, Irina A; Vortmeyer, Alexander O; Rodgers, Griffin P; Oldfield, Edward H; Lonser, Russell R.

Afiliación

Park DM; Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, United States of America.

PLoS Med ; 4(2): e60, 2007 Feb.

Article en En | MEDLINE | ID: mdl-17298169

RESUMEN

BACKGROUND: To determine the origin of the neoplastic cell in central nervous system (CNS) hemangioblastomas in von Hippel-Lindau disease (VHL) and its role in tumor formation and distribution, we characterized and differentiated neoplastic cells from hemangioblastomas removed from VHL patients. METHODS AND FINDINGS: A total of 31 CNS hemangioblastomas from 25 VHL patients were resected and analyzed. Tumor cells from the hemangioblastomas were characterized, grown, and differentiated into multiple lineages. Resected hemangioblastomas were located in the cerebellum (11 tumors), brainstem (five tumors), and spinal cord (15 tumors). Consistent with an embryologically derived hemangioblast, the neoplastic cells demonstrated coexpression of the mesodermal markers brachyury, Flk-1 (vascular endothelial growth factor-2), and stem cell leukemia (Scl). The neoplastic cells also expressed hematopoietic stem cell antigens and receptors including CD133, CD34, c-kit, Scl, erythropoietin, and erythropoietin receptor. Under specific microenvironments, neoplastic cells (hemangioblasts) were expanded and differentiated into erythrocytic, granulocytic, and endothelial progenitors. Deletion of the wild-type VHL allele in the hematopoietic and endothelial progeny confirmed their neoplastic origin. CONCLUSIONS: The neoplastic cell of origin for CNS hemangioblastomas in VHL patients is the mesoderm-derived, embryologically arrested hemangioblast. The hematopoietic and endothelial differentiation potential of these cells can be reactivated under suitable conditions. These findings may also explain the unique tissue distribution of tumor involvement.

Asunto(s)

Neoplasias Cerebelosas/patología; Hemangioblastoma/patología; Células Madre Multipotentes/patología; Enfermedad de von Hippel-Lindau/complicaciones; Adolescente; Adulto; Western Blotting; Antígenos CD13/genética; Degranulación de la Célula; Neoplasias Cerebelosas/complicaciones; Femenino; Estudios de Seguimiento; Regulación Neoplásica de la Expresión Génica; Hemangioblastoma/complicaciones; Hemangioblastoma/cirugía; Humanos; Masculino; Persona de Mediana Edad; ARN Neoplásico/genética; Estudios Retrospectivos; Reacción en Cadena de la Polimerasa de Transcriptasa Inversa; Células Tumorales Cultivadas; Enfermedad de von Hippel-Lindau/patología

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Cerebelosas / Hemangioblastoma / Células Madre Multipotentes / Enfermedad de von Hippel-Lindau Tipo de estudio: Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Adolescent / Adult / Female / Humans / Male / Middle aged Idioma: En Revista: PLoS Med Asunto de la revista: MEDICINA Año: 2007 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos

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