title: Secreted protein acidic and rich in cysteine (SPARC) suppresses angiogenesis by down-regulating the expression of VEGF and MMP-7 in gastric cancer.
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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  SPARC suppresses angiogenesis of gastric cancer by down-regulating the expression of VEGF and MMP-7.
authors.affiliation: Department of General Surgery, Peking University First Hospital, Beijing, People's Republic of China.
authors.forename: Jun-Ling
authors.initials: JL
authors.lastname: Zhang
authors.forename: Guo-Wei
authors.initials: GW
authors.lastname: Chen
authors.forename: Yu-Cun
authors.initials: YC
authors.lastname: Liu
authors.forename: Peng-Yuan
authors.initials: PY
authors.lastname: Wang
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.forename: Yuan-Lian
authors.initials: YL
authors.lastname: Wan
authors.forename: Jing
authors.initials: J
authors.lastname: Zhu
authors.forename: Hong-Qiao
authors.initials: HQ
authors.lastname: Gao
authors.forename: Jie
authors.initials: J
authors.lastname: Yin
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Mao-Lin
authors.initials: ML
authors.lastname: Tian
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006023:Glycoproteins / Q000502:physiology*; D006801:Humans; D020783:Matrix Metalloproteinase 7 / Q000096:biosynthesis*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic; D015676:Osteonectin; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000201:enzymology*; D025521:Tumor Suppressor Proteins / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis*
chemical_list: D006023:Glycoproteins; D015676:Osteonectin; C577241:SPARC protein, human; C578250:SPARC protein, mouse; D025521:Tumor Suppressor Proteins; D042461:Vascular Endothelial Growth Factor A; D020783:Matrix Metalloproteinase 7