Hemangioblastoma-associated mast cells in von Hippel-Lindau disease are tumor derived

Merrill, Marsha J.; Edwards, Nancy A.; Lonser, Russell R.

doi:10.1182/blood-2012-08-452151

Cited by 7 publications

(2 citation statements)

References 6 publications

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“…The related studies are associated with the vascular progenitors including embryonic cells, reactive endothelial cells, stromal cells, and mast cells etc 5, 6 . In recent years, increasing evidence has showed that many mesodermal makers were expressed in both sporadic and inherited HBs 7, 8 , suggesting that HB-neovascularization is a similar embryologic vasculogenesis 9–12 .…”

Section: Introductionmentioning

confidence: 99%

Endothelial cells by inactivation of VHL gene direct angiogenesis, not vasculogenesis via Twist1 accumulation associated with hemangioblastoma neovascularization

Wáng

Chen

et al. 2017

Sci Rep

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Inactivation of the VHL tumour suppressor gene is a highly frequent genetic event in the carcinogenesis of central nervous system-(CNS) hemangioblastomas (HBs). The patterning of the similar embryonicvasculogenesis is an increasing concern in HB-neovascularization, and the classic vascular endothelial growth factor (VEGF)-mediated angiogenesis driven by VHL loss-of-function from human endothelium have been questioned. With this regard, we identify a distinct, VHL silencing-driven mechanism in which human vascular endothelial cells by means of increasing cell proliferation and decreasing cell apoptosis, is concomitant with facilitating accumulation of Twist1 protein in vascular endothelial cells in vitro. Importantly, this molecular mechanism is also pinpointed in CNS-HBs, and associated with the process of HB-neovascularization. In contrast with recent studies of HB-neovascularization, these modified cells did not endow with the typical features of vasculogenesis, indicating that this is a common angiogenesis implementing the formation of the vascular network. Taken together, these findings suggest that vasculogenesis and angiogenesis may constitute complementary mechanisms for HB-neovascularization, and could provide a rational recognition of single anti-angiogenic intervention including targeting to the Twist1 signalling for HBs.Hemangioblastomas (HBs) are high-vascularized neoplasms commonly arising in the cerebellum or brainstem [1][2][3][4] . The cytological origin and process of neovascularization remains tremendously controversial. Etiologically, HBs are divided into two subtypes, the sporadic HBs (takes up 75%) and familial HBs (VHL disease) (takes up 25%). Histologic examination showed numerous small capillary channels and abundant vacuolated 'stromal cells' in sporadic HBs and VHL-HBs 2 . Currently, surgical complete resection is the only curative treatment for sporadic HBs; however, surgical treatment of brain-stem HBs is a great challenge to neurosurgeons because of the location of HBs. Moreover, as an inherited multisystem disorder, VHL-HBs are difficult to be cured. So a better understanding of HB biological mechanisms may further provide useful insights into its therapeutic strategies.The cytological origin of HBs (including its neovascularization) and its evolutionary process remain controversial for nearly a century. The related studies are associated with the vascular progenitors including embryonic cells, reactive endothelial cells, stromal cells, and mast cells etc 5,6 . In recent years, increasing evidence has showed that many mesodermal makers were expressed in both sporadic and inherited HBs 7,8 , suggesting that HB-neovascularization is a similar embryologic vasculogenesis [9][10][11][12] . Then, as the classic hypothesis of HB-angiogenesis, the vascular endothelial growth factor (VEGF) secreted by stromal cells may bind to endothelial cells and trigger an intracellular signaling pathway in the endothelial cells that eventually results in cell proliferation and vascular formation 13 . In ...

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Section: Introductionmentioning

confidence: 99%

Endothelial cells by inactivation of VHL gene direct angiogenesis, not vasculogenesis via Twist1 accumulation associated with hemangioblastoma neovascularization

Wáng

Chen

et al. 2017

Sci Rep

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“…Dr. Lindau proposed that the hemangioblastomatous tissue may derive from a "congenital anlage" and hypothesized that the neoplastic cells are histologically similar to an "…embryological type of the tumor cells." 13 16,18 Dr. Lindau began studying angiomatosis retinae, a rare malady with familial tendency of which some 50 cases had been reported previously, which he believed were related to the cerebellar cysts he had observed in cadavers. While reviewing these cases, he found that approximately 20% of the patients had also been known to have intracranial complications.…”

Section: Formation Of the Thesismentioning

confidence: 99%

Dr. Arvid Lindau and discovery of von Hippel-Lindau disease

Huntoon

Oldfield

Lonser

2015

JNS

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Arvid Lindau, MD, PhD, consolidated the disparate array of benign and malignant visceral and nervous system lesions into the neoplastic syndrome known as von Hippel-Lindau (VHL) disease. Based on this pioneering work, Dr. Lindau was awarded both a Rockefeller fellowship to work in Dr. Harvey Cushing's laboratory in Boston, Massachusetts, and the Lennmalm Prize. While working in Dr. Cushing's laboratory, Dr. Lindau continued his study of CNS hemangioblastomas. His work with Dr. Cushing led to their lifelong friendship and scientific collaboration. In this paper the authors describe Arvid Lindau's pioneering work in nervous system tumor pathology, his relationship to Dr. Cushing, and his role in advancing neurological surgery and research in Europe.

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