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学科主题: 临床医学
题名:
Secreted Protein Acidic and Rich in Cysteine (SPARC) Suppresses Angiogenesis by Down-Regulating the Expression of VEGF and MMP-7 in Gastric Cancer
作者: 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
发表日期: 2012-09-05
DOI: 10.1371/journal.pone.0044618
卷: 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
所属项目编号: 30901417/H1617
项目资助者: National Natural Science Foundation of China
WOS记录号: WOS:000308463800083
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/51136
Appears in Collections:北京大学第一临床医学院_普通外科_期刊论文

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作者单位: Peking Univ, Dept Gen Surg, Hosp 1, Beijing 100871, Peoples R China

Recommended Citation:
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).
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