Canstatin represses glioma growth by inhibiting formation of VM-like structures

Vasculogenic mimicry (VM) is different from classical tumor angiogenesis and does not depend on endothelial cells. VM is closely related to the prognosis of various cancers. Canstatin was first identified as an endogenous angiogenesis inhibitor. In the present study, the inhibitory effect of canstat...

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Main Authors: Ma Yuqiang, Wu Tao, Zhou Houjie, He Guilu, Li Yifei, Wang Bocheng, Guo Qiang, Chen Baodong, Li Weiping
Format: Article
Language:English
Published: De Gruyter 2021-08-01
Series:Translational Neuroscience
Subjects:
Online Access:https://doi.org/10.1515/tnsci-2020-0176
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author Ma Yuqiang
Wu Tao
Zhou Houjie
He Guilu
Li Yifei
Wang Bocheng
Guo Qiang
Chen Baodong
Li Weiping
author_facet Ma Yuqiang
Wu Tao
Zhou Houjie
He Guilu
Li Yifei
Wang Bocheng
Guo Qiang
Chen Baodong
Li Weiping
author_sort Ma Yuqiang
collection DOAJ
description Vasculogenic mimicry (VM) is different from classical tumor angiogenesis and does not depend on endothelial cells. VM is closely related to the prognosis of various cancers. Canstatin was first identified as an endogenous angiogenesis inhibitor. In the present study, the inhibitory effect of canstatin on VM formation was evaluated. Human glioblastoma cell lines U87 and U251 were letivirally transduced to overexpress canstatin gene or GFP as control. In vitro assays showed that canstatin overexpression reduced the tube formation of U87 and U251 cells in Matrigel. A xenograft glioma model was created by subcutaneous injection of lentivirally modified U87 cells into nude mice. The results of in vivo experiments showed that canstatin gene introduction inhibited the growth of glioma xenografts. In tumor xenografts overexpressing canstatin, U87-mediated formation of VM-like structures and VM-related VEGF (vascular endothelial growth factor) expression were remarkably reduced. Canstatin overexpression also decreased the phosphorylation of Akt and reduced the expression of Survivin in vitro. In addition, HIF-1α production and MMP-2 secretion were decreased by canstatin overexpression. Therefore, these results suggested a protective role of canstatin during VM-like structure formation of glioma probably via inhibiting signaling pathways inducing vasculogenic mimicry.
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spelling doaj.art-56cf1f4e838a44e8a0f2771f6e03528a2022-12-22T04:21:21ZengDe GruyterTranslational Neuroscience2081-69362021-08-0112130931910.1515/tnsci-2020-0176Canstatin represses glioma growth by inhibiting formation of VM-like structuresMa Yuqiang0Wu Tao1Zhou Houjie2He Guilu3Li Yifei4Wang Bocheng5Guo Qiang6Chen Baodong7Li Weiping8Neurosurgery Department, Peking University Shenzhen Hospital, 1120 Lianhua Road, Futian District, Shenzhen 518035, People’s Republic of ChinaNeurosurgery Department, Peking University Shenzhen Hospital, 1120 Lianhua Road, Futian District, Shenzhen 518035, People’s Republic of ChinaNeurosurgery Department, Peking University Shenzhen Hospital, 1120 Lianhua Road, Futian District, Shenzhen 518035, People’s Republic of ChinaGuangDong 999 Brain Hospital, Guangzhou 510510, People’s Republic of ChinaNeurosurgery Department, Peking University Shenzhen Hospital, 1120 Lianhua Road, Futian District, Shenzhen 518035, People’s Republic of ChinaNeurosurgery Department, Peking University Shenzhen Hospital, 1120 Lianhua Road, Futian District, Shenzhen 518035, People’s Republic of ChinaNeurosurgery Department, Peking University Shenzhen Hospital, 1120 Lianhua Road, Futian District, Shenzhen 518035, People’s Republic of ChinaNeurosurgery Department, Peking University Shenzhen Hospital, 1120 Lianhua Road, Futian District, Shenzhen 518035, People’s Republic of ChinaNeurosurgery Department, Shenzhen Second People’s Hospital, Sungang Road, Futian District, Guangzhou 510510, People’s Republic of ChinaVasculogenic mimicry (VM) is different from classical tumor angiogenesis and does not depend on endothelial cells. VM is closely related to the prognosis of various cancers. Canstatin was first identified as an endogenous angiogenesis inhibitor. In the present study, the inhibitory effect of canstatin on VM formation was evaluated. Human glioblastoma cell lines U87 and U251 were letivirally transduced to overexpress canstatin gene or GFP as control. In vitro assays showed that canstatin overexpression reduced the tube formation of U87 and U251 cells in Matrigel. A xenograft glioma model was created by subcutaneous injection of lentivirally modified U87 cells into nude mice. The results of in vivo experiments showed that canstatin gene introduction inhibited the growth of glioma xenografts. In tumor xenografts overexpressing canstatin, U87-mediated formation of VM-like structures and VM-related VEGF (vascular endothelial growth factor) expression were remarkably reduced. Canstatin overexpression also decreased the phosphorylation of Akt and reduced the expression of Survivin in vitro. In addition, HIF-1α production and MMP-2 secretion were decreased by canstatin overexpression. Therefore, these results suggested a protective role of canstatin during VM-like structure formation of glioma probably via inhibiting signaling pathways inducing vasculogenic mimicry.https://doi.org/10.1515/tnsci-2020-0176gliomacanstatinvasculogenic mimicryu87vegfhif-1α
spellingShingle Ma Yuqiang
Wu Tao
Zhou Houjie
He Guilu
Li Yifei
Wang Bocheng
Guo Qiang
Chen Baodong
Li Weiping
Canstatin represses glioma growth by inhibiting formation of VM-like structures
Translational Neuroscience
glioma
canstatin
vasculogenic mimicry
u87
vegf
hif-1α
title Canstatin represses glioma growth by inhibiting formation of VM-like structures
title_full Canstatin represses glioma growth by inhibiting formation of VM-like structures
title_fullStr Canstatin represses glioma growth by inhibiting formation of VM-like structures
title_full_unstemmed Canstatin represses glioma growth by inhibiting formation of VM-like structures
title_short Canstatin represses glioma growth by inhibiting formation of VM-like structures
title_sort canstatin represses glioma growth by inhibiting formation of vm like structures
topic glioma
canstatin
vasculogenic mimicry
u87
vegf
hif-1α
url https://doi.org/10.1515/tnsci-2020-0176
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