SPARC expression is negatively correlated with clinicopathological factors of gastric cancer and inhibits malignancy of gastric cancer cells

Zhang,Junling; Wang,Pengyuan; Zhu,Jing; Wang,Wei; Yin,Jie; Zhang,Chi; Chen,Ziyi; Sun,Lie; Wan,Yuanlian; Wang,Xin; Chen,Guowei; Liu,Yucun

doi:10.3892/or.2014.3118

SPARC expression is negatively correlated with clinicopathological factors of gastric cancer and inhibits malignancy of gastric cancer cells

Authors:
- Junling Zhang
- Pengyuan Wang
- Jing Zhu
- Wei Wang
- Jie Yin
- Chi Zhang
- Ziyi Chen
- Lie Sun
- Yuanlian Wan
- Xin Wang
- Guowei Chen
- Yucun Liu
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Affiliations: Department of General Surgery, Peking University First Hospital, Beijing 100034, P.R. China, Department of General Surgery, Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China
Published online on: March 27, 2014 https://doi.org/10.3892/or.2014.3118
Pages: 2312-2320

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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.

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