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Sox7 promotes high-grade glioma by increasing VEG FR2-mediated vascular abnormality

Cited 11 time in webofscience Cited 13 time in scopus
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Title
Sox7 promotes high-grade glioma by increasing VEG FR2-mediated vascular abnormality
Author(s)
IL-Kug Kim; Kangsan Kim; Eunhyeong Lee; Dongsun Oh; Chan soon Park; Seongeol Park; Jee myung Yang; Ju-hee Kim; Hyung-seok Kim; Shima, DT; Jeong hoon Kim; Seok ho Hong; Young hyun Cho; Young Hoon Kim; Jong bae Park; Gou Young Koh; Young Seok Ju; Heung Kyu Lee; Seung Joo Lee; Injune Kim
Publication Date
2018-03
Journal
JOURNAL OF EXPERIMENTAL MEDICINE, v.215, no.3, pp.963 - 983
Publisher
ROCKEFELLER UNIV PRESS
Abstract
High-grade glioma (HGG) is highly angiogenic, but antiangiogenic therapy has transient clinical benefit in only a fraction of patients. Vascular regulators of these heterogeneous responses remain undetermined. We found up-regulation of Sox7 and down-regulation of Sox17 in tumor endothelial cells (tECs) in mouse HGG. Sox7 deletion suppressed VEG FR2 expression, vascular abnormality, hypoxia-driven invasion, regulatory T cell infiltration, and tumor growth. Conversely, Sox17 deletion exacerbated these phenotypes by up-regulating Sox7 in tECs. Anti-VEG FR2 antibody treatment delayed tumor growth by normalizing Sox17-deficient abnormal vessels with high Sox7 levels but promoted it by regressing Sox7-deficient vessels, recapitulating variable therapeutic responses to antiangiogenic therapy in HGG patients. Our findings establish that Sox7 promotes tumor growth via vessel abnormalization, and its level determines the therapeutic outcome of VEG FR2 inhibition in HGG. In 189 HGG patients, Sox7 expression was heterogeneous in tumor vessels, and high Sox7 levels correlated with poor survival, early recurrence, and impaired vascular function, emphasizing the clinical relevance of Sox7 in HGG. ⓒ 2018 Kim et al.
URI
https://pr.ibs.re.kr/handle/8788114/4996
DOI
10.1084/jem.20170123
ISSN
0022-1007
Appears in Collections:
Center for Vascular Research(혈관 연구단) > 1. Journal Papers (저널논문)
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