原创力文档secreted protein acidic and rich in cysteine (sparc) suppresses angiogenesis by down-regulating the expression of vegf and mmp-7 in gastric cancer分泌蛋白的酸性和富含半胱氨酸(sparc)抑制血管生成显示vegf的表达和mmp-7胃癌.pdfVIP
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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分泌蛋白的酸性和富含半胱氨酸(sparc)抑制血管生成显示vegf的表达和mmp-7胃癌
Secreted Protein Acidic and Rich in Cysteine (SPARC)
Suppresses Angiogenesis by Down-Regulating the
Expression of VEGF and MMP-7 in Gastric Cancer
Jun-Ling Zhang., Guo-Wei Chen., Yu-Cun Liu*, Peng-Yuan Wang, Xin Wang, Yuan-Lian Wan, Jing Zhu,
Hong-Qiao Gao, Jie Yin, Wei Wang, Mao-Lin Tian
Department of General Surgery, Peking University First Hospital, Beijing, People’s Republic of China
Abstract
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
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