Endothelial cell-specific reduction of heparan sulfate suppresses glioma growth in mice

Abstract Purpose Heparan sulfate (HS) is one of the factors that has been suggested to be associated with angiogenesis and invasion of glioblastoma (GBM), an aggressive and fast-growing brain tumor. However, it remains unclear how HS of endothelial cells is involved in angiogenesis in glioblastoma a...

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Autores principales:	Takamasa Kinoshita, Hiroyuki Tomita, Hideshi Okada, Ayumi Niwa, Fuminori Hyodo, Tomohiro Kanayama, Mikiko Matsuo, Yuko Imaizumi, Takahiro Kuroda, Yuichiro Hatano, Masafumi Miyai, Yusuke Egashira, Yukiko Enomoto, Noriyuki Nakayama, Shigeyuki Sugie, Kazu Matsumoto, Yu Yamaguchi, Masayuki Matsuo, Hideaki Hara, Toru Iwama, Akira Hara
Formato:	article
Lenguaje:	EN
Publicado:	Springer 2021
Materias:	Glioblastoma Angiogenesis Heparan sulfate Fibroblast growth factor 2 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/b5d26bf40ce2496e8e351218cdfaeb3c
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spelling	oai:doaj.org-article:b5d26bf40ce2496e8e351218cdfaeb3c2021-11-14T12:44:37ZEndothelial cell-specific reduction of heparan sulfate suppresses glioma growth in mice10.1007/s12672-021-00444-32730-6011https://doaj.org/article/b5d26bf40ce2496e8e351218cdfaeb3c2021-11-01T00:00:00Zhttps://doi.org/10.1007/s12672-021-00444-3https://doaj.org/toc/2730-6011Abstract Purpose Heparan sulfate (HS) is one of the factors that has been suggested to be associated with angiogenesis and invasion of glioblastoma (GBM), an aggressive and fast-growing brain tumor. However, it remains unclear how HS of endothelial cells is involved in angiogenesis in glioblastoma and its prognosis. Thus, we investigated the effect of endothelial cell HS on GBM development. Methods We generated endothelial cell-specific knockout of Ext1, a gene encoding a glycosyltransferase and essential for HS synthesis, and murine GL261 glioblastoma cells were orthotopically transplanted. Two weeks after transplantation, we examined the tumor progression and underlying mechanisms. Results The endothelial cell-specific Ext1 knockout (Ext1 CKO ) mice exhibited reduced HS expression specifically in the vascular endothelium of the brain capillaries compared with the control wild-type (WT) mice. GBM growth was significantly suppressed in Ext1 CKO mice compared with that in WT mice. After GBM transplantation, the survival rate was significantly higher in Ext1 CKO mice than in WT mice. We investigated how the effect of fibroblast growth factor 2 (FGF2), which is known as an angiogenesis-promoting factor, differs between Ext1 CKO and WT mice by using an in vivo Matrigel assay and demonstrated that endothelial cell-specific HS reduction attenuated the effect of FGF2 on angiogenesis. Conclusions HS reduction in the vascular endothelium of the brain suppressed GBM growth and neovascularization in mice.Takamasa KinoshitaHiroyuki TomitaHideshi OkadaAyumi NiwaFuminori HyodoTomohiro KanayamaMikiko MatsuoYuko ImaizumiTakahiro KurodaYuichiro HatanoMasafumi MiyaiYusuke EgashiraYukiko EnomotoNoriyuki NakayamaShigeyuki SugieKazu MatsumotoYu YamaguchiMasayuki MatsuoHideaki HaraToru IwamaAkira HaraSpringerarticleGlioblastomaAngiogenesisHeparan sulfateFibroblast growth factor 2Neoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENDiscover Oncology, Vol 12, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Glioblastoma Angiogenesis Heparan sulfate Fibroblast growth factor 2 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Glioblastoma Angiogenesis Heparan sulfate Fibroblast growth factor 2 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Takamasa Kinoshita Hiroyuki Tomita Hideshi Okada Ayumi Niwa Fuminori Hyodo Tomohiro Kanayama Mikiko Matsuo Yuko Imaizumi Takahiro Kuroda Yuichiro Hatano Masafumi Miyai Yusuke Egashira Yukiko Enomoto Noriyuki Nakayama Shigeyuki Sugie Kazu Matsumoto Yu Yamaguchi Masayuki Matsuo Hideaki Hara Toru Iwama Akira Hara Endothelial cell-specific reduction of heparan sulfate suppresses glioma growth in mice
description	Abstract Purpose Heparan sulfate (HS) is one of the factors that has been suggested to be associated with angiogenesis and invasion of glioblastoma (GBM), an aggressive and fast-growing brain tumor. However, it remains unclear how HS of endothelial cells is involved in angiogenesis in glioblastoma and its prognosis. Thus, we investigated the effect of endothelial cell HS on GBM development. Methods We generated endothelial cell-specific knockout of Ext1, a gene encoding a glycosyltransferase and essential for HS synthesis, and murine GL261 glioblastoma cells were orthotopically transplanted. Two weeks after transplantation, we examined the tumor progression and underlying mechanisms. Results The endothelial cell-specific Ext1 knockout (Ext1 CKO ) mice exhibited reduced HS expression specifically in the vascular endothelium of the brain capillaries compared with the control wild-type (WT) mice. GBM growth was significantly suppressed in Ext1 CKO mice compared with that in WT mice. After GBM transplantation, the survival rate was significantly higher in Ext1 CKO mice than in WT mice. We investigated how the effect of fibroblast growth factor 2 (FGF2), which is known as an angiogenesis-promoting factor, differs between Ext1 CKO and WT mice by using an in vivo Matrigel assay and demonstrated that endothelial cell-specific HS reduction attenuated the effect of FGF2 on angiogenesis. Conclusions HS reduction in the vascular endothelium of the brain suppressed GBM growth and neovascularization in mice.
format	article
author	Takamasa Kinoshita Hiroyuki Tomita Hideshi Okada Ayumi Niwa Fuminori Hyodo Tomohiro Kanayama Mikiko Matsuo Yuko Imaizumi Takahiro Kuroda Yuichiro Hatano Masafumi Miyai Yusuke Egashira Yukiko Enomoto Noriyuki Nakayama Shigeyuki Sugie Kazu Matsumoto Yu Yamaguchi Masayuki Matsuo Hideaki Hara Toru Iwama Akira Hara
author_facet	Takamasa Kinoshita Hiroyuki Tomita Hideshi Okada Ayumi Niwa Fuminori Hyodo Tomohiro Kanayama Mikiko Matsuo Yuko Imaizumi Takahiro Kuroda Yuichiro Hatano Masafumi Miyai Yusuke Egashira Yukiko Enomoto Noriyuki Nakayama Shigeyuki Sugie Kazu Matsumoto Yu Yamaguchi Masayuki Matsuo Hideaki Hara Toru Iwama Akira Hara
author_sort	Takamasa Kinoshita
title	Endothelial cell-specific reduction of heparan sulfate suppresses glioma growth in mice
title_short	Endothelial cell-specific reduction of heparan sulfate suppresses glioma growth in mice
title_full	Endothelial cell-specific reduction of heparan sulfate suppresses glioma growth in mice
title_fullStr	Endothelial cell-specific reduction of heparan sulfate suppresses glioma growth in mice
title_full_unstemmed	Endothelial cell-specific reduction of heparan sulfate suppresses glioma growth in mice
title_sort	endothelial cell-specific reduction of heparan sulfate suppresses glioma growth in mice
publisher	Springer
publishDate	2021
url	https://doaj.org/article/b5d26bf40ce2496e8e351218cdfaeb3c
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Endothelial cell-specific reduction of heparan sulfate suppresses glioma growth in mice

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