Tumor derived vasculogenesis in von Hippel-Lindau disease-associated tumors.

[von hippel-lindau disease]

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 UMRC 6 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 .