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Inhibition of intracranial hemangioma growth and hemorrhage by TNFSF15
Author(s) -
Yang GuiLi,
Han Zhenying,
Xiong Jianhua,
Wang Shizhao,
Wei Huijie,
Qin TingTing,
Xiao Huaiyuan,
Liu Ye,
Xu LiXia,
Qi JianWei,
Zhang ZhiSong,
Jiang Rongcai,
Zhang Jianning,
Li LuYuan
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201802758rrr
Subject(s) - pericyte , infiltration (hvac) , cytokine , pathology , medicine , vascular endothelial growth factor , hemangioma , cancer research , immunology , biology , endothelial stem cell , vegf receptors , biochemistry , physics , in vitro , thermodynamics
Hemangioblastoma (HB) is an abnormal intracranial buildup of blood vessels that exhibit a great potential for hemorrhage. Surgical options are limited, and few medications are available for treatment. We show here by immunohistochemical analysis that HB lesions display highly increased levels of VEGF expression and macrophage/microglia infiltration compared with those in normal brain tissues. In the meantime, TNF superfamily 15 (TNFSF15) (also known as vascular endothelial growth inhibitor), an antiangiogenic cytokine, is highly expressed in normal brain blood vessels but diminished in HB lesions. We set up a brain hemangioma model by using mouse bEnd.3 cells of a T antigen—transformed endothelial cell line that produce a large amount of VEGF. When implanted in mouse brains, these cells form lesions that closely resemble the pathologic characteristics of HB. Retroviral infection of bEnd.3 cells with TNFSF15 leads to inhibition of VEGF production and retardation of hemangioma formation. Similar results are obtained when wild‐type bEnd.3 cells are implanted in the brains of transgenic mice overexpressing TNFSF15. Additionally, TNFSF15 treatment results in enhanced pericyte coverage of the blood vessels in the lesions together with reduced inflammatory cell infiltration and decreased hemorrhage. These findings indicate that the ability of TNFSF15 to counterbalance the abnormally highly angiogenic and inflammatory potential of the microenvironment of HB is of therapeutic value for the treatment of this disease.—Yang, G.‐L., Han, Z., Xiong, J., Wang, S., Wei, H., Qin, T.‐T., Xiao, H., Liu, Y., Xu, L.‐X., Qi, J.‐W., Zhang, Z.‐S., Jiang, R., Zhang, J., Li, L.‐Y. Inhibition of intracranial hemangioma growth and hemorrhage by TNFSF15. FASEB J. 33, 10505–10514 (2019). www.fasebj.org