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Secreted Protein Acidic and Rich in Cysteine (SPARC) Suppresses Angiogenesis by Down-Regulating the Expression of VEGF and MMP-7 in Gastric Cancer
Zhang, Jun-Ling; Chen, Guo-Wei; Liu, Yu-Cun; Wang, Peng-Yuan; Wang, Xin; Wan, Yuan-Lian; Zhu, Jing; Gao, Hong-Qiao; Yin, Jie; Wang, Wei; Tian, Mao-Lin
刊名PLOS ONE
2012-09-05
DOI10.1371/journal.pone.0044618
7期:9
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Multidisciplinary Sciences
研究领域[WOS]Science & Technology - Other Topics
关键词[WOS]ENDOTHELIAL GROWTH-FACTOR ; OVARIAN-CANCER ; DIFFERENTIAL EXPRESSION ; PROGRESSION ; CELLS ; CARCINOMA ; BIOLOGY
英文摘要

Background: 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.

Method: 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.

Results: 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.

Conclusion: SPARC suppresses angiogenesis of gastric cancer by down-regulating the expression of VEGF and MMP-7.

语种英语
WOS记录号WOS:000308463800083
引用统计
被引频次:20[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/51136
专题北京大学第一临床医学院_普通外科
作者单位Peking Univ, Dept Gen Surg, Hosp 1, Beijing 100871, Peoples R China
推荐引用方式
GB/T 7714
Zhang, Jun-Ling,Chen, Guo-Wei,Liu, Yu-Cun,et al. Secreted Protein Acidic and Rich in Cysteine (SPARC) Suppresses Angiogenesis by Down-Regulating the Expression of VEGF and MMP-7 in Gastric Cancer[J]. PLOS ONE,2012,7(9).
APA Zhang, Jun-Ling.,Chen, Guo-Wei.,Liu, Yu-Cun.,Wang, Peng-Yuan.,Wang, Xin.,...&Tian, Mao-Lin.(2012).Secreted Protein Acidic and Rich in Cysteine (SPARC) Suppresses Angiogenesis by Down-Regulating the Expression of VEGF and MMP-7 in Gastric Cancer.PLOS ONE,7(9).
MLA Zhang, Jun-Ling,et al."Secreted Protein Acidic and Rich in Cysteine (SPARC) Suppresses Angiogenesis by Down-Regulating the Expression of VEGF and MMP-7 in Gastric Cancer".PLOS ONE 7.9(2012).
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