title: SPARC expression is negatively correlated with clinicopathological factors of gastric cancer and inhibits malignancy of gastric cancer cells.
abstract: Secreted protein acidic and rich in cysteine (SPARC) is a glycoprotein which plays multiple roles in different types of cancer. Our previous study showed that SPARC overexpression inhibited the growth and angiogenesis of tumors, and reduced expression of vascular endothelial growth factor (VEGF). However, the relationship between SPARC expression and clinicopathological factors of gastric cancer (GC) is controversial, and the role of SPARC in GC remains unclear. We evaluated expression of SPARC in 65 human GC tissues using immunohistochemistry (IHC). The results indicated that SPARC expression was negatively correlated with clinicopathological factors of GC. In vitro assay showed that SPARC overexpression decreased proliferation and clonogenicity by suppressing CD44 expression. In addition, SPARC overexpression inhibited VEGF induced proliferation and arrested cell cycle of GC cells by reducing the activation of VEGFR2, ERK1/2 and AKT signaling pathways. SPARC suppressed the invasion and migration of GC by reducing MMP-7, MMP-9, N-cadherin, Sp1 and p-ERK1/2 expression. In the in vivo assay, cancer metastasis mouse models were established by tail vein injection. The results revealed that the lung metastases of SPARC-overexpressing GC cells in the mice were much fewer than those of control cells.
authors.affiliation: Department of General Surgery, Peking University First Hospital, Beijing 100034, P.R. China.
authors.forename: Junling
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, Peking University First Hospital, Beijing 100034, P.R. China.
authors.forename: Pengyuan
authors.initials: P
authors.lastname: Wang
authors.affiliation: Department of General Surgery, Peking University First Hospital, Beijing 100034, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Department of General Surgery, Peking University First Hospital, Beijing 100034, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of General Surgery, Peking University First Hospital, Beijing 100034, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Yin
authors.affiliation: Department of General Surgery, Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China.
authors.forename: Chi
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, Peking University First Hospital, Beijing 100034, P.R. China.
authors.forename: Ziyi
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of General Surgery, Peking University First Hospital, Beijing 100034, P.R. China.
authors.forename: Lie
authors.initials: L
authors.lastname: Sun
authors.affiliation: Department of General Surgery, Peking University First Hospital, Beijing 100034, P.R. China.
authors.forename: Yuanlian
authors.initials: Y
authors.lastname: Wan
authors.affiliation: Department of General Surgery, Peking University First Hospital, Beijing 100034, P.R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of General Surgery, Peking University First Hospital, Beijing 100034, P.R. China.
authors.forename: Guowei
authors.initials: G
authors.lastname: Chen
authors.affiliation: Department of General Surgery, Peking University First Hospital, Beijing 100034, P.R. China.
authors.forename: Yucun
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000368:Aged; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D015820:Cadherins / Q000096:biosynthesis; D059447:Cell Cycle Checkpoints; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D018960:Hyaluronan Receptors / Q000096:biosynthesis; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000556:secondary; D008207:Lymphatic Metastasis / Q000235:genetics; D020935:MAP Kinase Signaling System; D008297:Male; D020783:Matrix Metalloproteinase 7 / Q000096:biosynthesis; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000235:genetics; D015676:Osteonectin / Q000096:biosynthesis* / Q000235:genetics*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011897:Random Allocation; D016329:Sp1 Transcription Factor / Q000096:biosynthesis; D013274:Stomach Neoplasms / Q000235:genetics / Q000473:pathology*; D014183:Transplantation, Heterologous; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000494:pharmacology; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000096:biosynthesis
chemical_list: D015703:Antigens, CD; C497483:CD44 protein, human; C050361:CDH2 protein, human; D015820:Cadherins; D018960:Hyaluronan Receptors; D015676:Osteonectin; C577241:SPARC protein, human; D016329:Sp1 Transcription Factor; C108209:SP1 protein, human; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C000588866:KDR protein, human; D040301:Vascular Endothelial Growth Factor Receptor-2; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; C060932:MMP7 protein, human; D020783:Matrix Metalloproteinase 7; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9