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. (Cancer Res 2006; 66(8): 4167-72)

RCAS/SCL-TVA Animal Model Allows Targeted Delivery of Polyoma Middle T Oncogene to Vascular Endothelial Progenitors In vivo and Results in Hemangioma Development

“…Considering that the cells originally infected with PyMT were likely to be early progenitors, which are present in very small numbers, the celerity of the disease points to a very efficient gene delivery system. This experimental system may be useful to model human pediatric hemangiomas, which are believed to be derived from embryonic hemanangioblasts (34,35). In fact, a high percentage of cells in human hemangioblastomas express SCL (34), which is consistent with the expression of SCL and TVA we observed in SCL-TVA hemangiomas.…”

“…This experimental system may be useful to model human pediatric hemangiomas, which are believed to be derived from embryonic hemanangioblasts (34,35). In fact, a high percentage of cells in human hemangioblastomas express SCL (34), which is consistent with the expression of SCL and TVA we observed in SCL-TVA hemangiomas. Furthermore, some of the lesions developed in SCL-TVA mice resemble those seen in Kasabach-Meritt syndrome, first described in an infant with a vascular anomaly that included microangiopathic hemolytic anemia, a consumptive coagulopathy, thrombocytopenia, and an enlarging vascular lesion (36,37).…”

Surgical management of cerebellar hemangioblastomas in patients with von Hippel–Lindau disease

“…Recent evidence suggests that this unique and highly conserved distribution pattern is the result of tumor development during embryogenesis. 18,56 Effect of Radiation. Because of the potential morbidity associated with resection of multiple CNS hemangioblastomas in VHL disease, radiation therapy has been used as an adjunct to or instead of resection.…”

Immune-related zinc finger gene ZFAT is an essential transcriptional regulator for hematopoietic differentiation in blood islands

“…D uring embryonic development, mesodermal progenitors give rise to hemangioblasts, which have a differentiation-potential for both endothelial and hematopoietic lineages (1)(2)(3). Hemangioblasts arise in the primitive streak and then migrate into the extraembryonic yolk sac to form blood islands (4,5).…”