Secreted protein acidic and rich in cysteine (SPARC) suppresses angiogenesis by down-regulating the expression of VEGF and MMP-7 in gastric cancer.
Secreted protein acidic and rich in cysteine (SPARC) suppresses angiogenesis by down-regulating the expression of VEGF and MMP-7 in gastric cancer.
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DOI：
10.1371/journal.pone.0044618
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Tian ML
中科院分区：
文献类型：
--
作者：
Zhang JL;Chen GW;Liu YC;Wang PY;Wang X;Wan YL;Zhu J;Gao HQ;Yin J;Wang W;Tian ML
富含半胱氨酸的酸性分泌蛋白（Cys）是一种糖蛋白，在不同类型的癌症中具有抑制血管生成、增殖和侵袭的功能。据信，VEGF调节新血管形成的能力部分是由其调节血管内皮生长因子（VEGF）和基质金属蛋白酶（MMP）表达的能力介导的。在这项研究中，我们的目的是确定在体外和体内的胃癌细胞中的增殖和血管生成的影响，表达的p53。我们评估了7个人胃癌细胞系中的表达。建立了稳定转染的过表达细胞系（BGC-SP）和稳定转染的敲低表达细胞系（HGC-sh）。通过检测体外HUVECs的毛细血管形成和体内背侧皮褶腔模型来研究过表达和沉默的影响。采用实时荧光定量PCR和蛋白质印迹法检测VEGF和MMP-7的表达是否受VEGF表达的调节。为进一步研究TGF-β 1表达对体内血管生成的影响，建立异种移植模型，免疫组化法检测不同克隆的微血管密度（MVD）。内源性VEGF过表达可抑制VEGF和MMP-7的表达，并抑制BGC-SP细胞诱导的血管生成。相应地，沉默VEGF和MMP-7的表达增加，以及由HGC-sh细胞诱导的血管生成。当VEGF被抗体中和时，HGC-sh细胞中的VEGF沉默诱导的血管生成升高降低，并且MMP-7在体外被敲低。胃癌组织中VEGF和MMP-7的表达下调，从而抑制胃癌血管生成。
Secreted protein acidic and rich in cysteine (SPARC) is a glycoprotein that functions to inhibit angiogenesis, proliferation, and invasion in different types of cancer. The ability of SPARC to modulate neovascularisation is believed to be mediated in part by its ability to modulate the expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs). In this study, we aimed to determine the effect of SPARC expression in gastric cancer cells on proliferation and angiogenesis in vitro and in vivo. We evaluated expression of SPARC in seven human gastric cancer cell lines. Then we established a stably transfected SPARC overexpressed cell line (BGC-SP) and a stably transfected SPARC knock-down cell line (HGC-sh). The effect of SPARC overexpression and SPARC silencing was studied by examining capillary formation of HUVECs in vitro and a dorsal skin-fold chamber model in vivo. Quantitative real-time PCR and western blotting were performed to detect if the expressions of VEGF and MMP-7 were modulated by SPARC expression. To further determine the effect of SPARC expression on angiogenesis in vivo, xenograft models were established and microvessel density (MVD) of different clones were detected by immunohistochemistry. Endogenous SPARC overexpression inhibited the expression of VEGF and MMP-7, as well as the angiogenesis induced by BGC-SP cells. Correspondingly, SPARC silencing increased the expression of VEGF and MMP-7, as well as the angiogenesis induced by HGC-sh cells. Elevated angiogenesis induced by SPARC silencing in HGC-sh cells was decreased when VEGF was neutralised by antibodies, and MMP-7 was knocked down in vitro. SPARC suppresses angiogenesis of gastric cancer by down-regulating the expression of VEGF and MMP-7.
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影响因子：
8.8
作者：
通讯作者：
--
影响因子：
6.4
作者：
Yunker, Christopher K.;Golembieski, William;Rempel, Sandra A.
通讯作者：
Rempel, Sandra A.
DOI：
10.1161/atvbaha.108.179663
发表时间：
2009-06-01
影响因子：
8.7
作者：
Ferrara, Napoleone
通讯作者：
Ferrara, Napoleone
影响因子：
2.8
作者：
Wang, Lifeng;Yang, Miling;Shan, Lihui;Qi, Lei;Chai, Cuicui;Zhou, Qiufeng;Yao, Ke;Wu, Hongmei;Sun, Wenguang
通讯作者：
Sun, Wenguang
影响因子：
8.8
作者：
Wang, CS;Lin, KH;Chen, SL;Chan, YF;Hsueh, S
通讯作者：
Hsueh, S