Developmental arrest of angioblastic lineage initiates tumorigenesis in von Hippel-Lindau disease.
The nature of the cell responsible for von Hippel-Lindau (VHL) disease-associated tumor formation has been controversial for decades. We demonstrate that VHL disease-associated central nervous system tumors are composed of developmentally arrested angioblasts that coexpress erythropoietin (Epo) and Epo receptor. The angioblasts are capable of differentiating into RBCs via formation of blood islands with extramedullary hematopoiesis. Because of VHL deficiency, Epo receptor-expressing, developmentally arrested angioblasts simultaneously coexpress Epo, which may represent a crucial pathogenetic step in tumor formation.
Vortmeyer
Alexander O
AO
Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke/NIH, 10 Center Drive, Bethesda, MD 20892, USA.
Frank
Stephan
S
Jeong
Seon-Yong
SY
Yuan
Kristy
K
Ikejiri
Barbara
B
Lee
Youn-Soo
YS
Bhowmick
Deb
D
Lonser
Russell R
RR
Smith
Reginald
R
Rodgers
Griffin
G
Oldfield
Edward H
EH
Zhuang
Zhengping
Z
D002528:Cerebellar Neoplasms / Q000209:etiology* / Q000378:metabolism / Q000473:pathology*; D004921:Erythropoietin / Q000096:biosynthesis / Q000378:metabolism; D018325:Hemangioblastoma / Q000209:etiology* / Q000378:metabolism / Q000473:pathology*; D006411:Hematopoiesis, Extramedullary; D006801:Humans; D007150:Immunohistochemistry; D017467:Receptors, Erythropoietin / Q000096:biosynthesis / Q000378:metabolism; D006623:von Hippel-Lindau Disease / Q000150:complications* / Q000235:genetics / Q000473:pathology*
D017467:Receptors, Erythropoietin; D004921:Erythropoietin