Endothelial cell-specific reduction of heparan sulfate suppresses glioma growth in mice.
Endothelial cell-specific reduction of heparan sulfate suppresses glioma growth in mice.
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DOI：
10.1007/s12672-021-00444-3
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发表时间：
2021
影响因子：
2.2
通讯作者：
Hara A
中科院分区：
文献类型：
--
作者：
Kinoshita T;Tomita H;Okada H;Niwa A;Hyodo F;Kanayama T;Matsuo M;Imaizumi Y;Kuroda T;Hatano Y;Miyai M;Egashira Y;Enomoto Y;Nakayama N;Sugie S;Matsumoto K;Yamaguchi Y;Matsuo M;Hara H;Iwama T;Hara A
硫酸乙酰肝素（HS）是被认为与血管生成和胶质母细胞瘤（GBM）侵袭有关的因素之一，胶质母细胞瘤是一种侵袭性和快速生长的脑肿瘤。然而，内皮细胞HS如何参与胶质母细胞瘤血管生成及其预后尚不清楚。因此，我们研究了内皮细胞HS对GBM发展的影响。我们产生了内皮细胞特异性敲除Ext1，这是一个编码糖基转移酶的基因，对HS合成至关重要，并将小鼠GL261胶质母细胞瘤细胞原位移植。移植后两周，我们检查了肿瘤的进展和潜在的机制。内皮细胞特异性Ext1敲除（Ext1CKO）小鼠与对照野生型（WT）小鼠相比，在脑毛细血管内皮中特异性表达HS降低。与WT小鼠相比，Ext1CKO小鼠的GBM生长明显受到抑制。在GBM移植后，Ext1CKO小鼠的存活率明显高于WT小鼠。我们通过体内Matrigel实验研究了成纤维细胞生长因子2 （FGF2）的作用在Ext1CKO和WT小鼠中是如何不同的，并证明内皮细胞特异性HS降低了FGF2对血管生成的影响。脑内血管内皮HS减少可抑制小鼠GBM生长和新生血管形成。在线版本包含补充材料，可在10.1007/s12672-021-00444-3获得。
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. 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. The endothelial cell-specific Ext1 knockout (Ext1CKO) 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 Ext1CKO mice compared with that in WT mice. After GBM transplantation, the survival rate was significantly higher in Ext1CKO 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 Ext1CKO 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. HS reduction in the vascular endothelium of the brain suppressed GBM growth and neovascularization in mice. The online version contains supplementary material available at 10.1007/s12672-021-00444-3.
影响因子：
5.2
作者：
Hatano T;Zhao S;Zhao Y;Nishijima K;Kuno N;Hanzawa H;Sakamoto T;Tamaki N;Kuge Y
通讯作者：
Kuge Y
缺氧的细胞周期分布和体内缺氧肿瘤细胞的进展。
影响因子：
8.8
作者：
Webster, L;Hodgkiss, R J;Wilson, G D
通讯作者：
Wilson, G D