Zhang Junling, Wang Pengyuan, Zhu Jing, Wang Wei, Yin Jie, Zhang Chi, Chen Ziyi, Sun Lie, Wan Yuanlian, Wang Xin, Chen Guowei, Liu Yucun
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.
Oncol Rep. 2014 May;31(5):2312-20. doi: 10.3892/or.2014.3118. Epub 2014 Mar 27.
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.
富含半胱氨酸的酸性分泌蛋白（SPARC）是一种糖蛋白，在不同类型的癌症中发挥多种作用。我们之前的研究表明，SPARC过表达抑制肿瘤的生长和血管生成，并降低血管内皮生长因子（VEGF）的表达。然而，SPARC表达与胃癌（GC）临床病理因素之间的关系存在争议，SPARC在GC中的作用仍不清楚。我们使用免疫组织化学（IHC）评估了65例人GC组织中SPARC的表达。结果表明，SPARC表达与GC的临床病理因素呈负相关。体外实验表明，SPARC过表达通过抑制CD44表达降低增殖和克隆形成能力。此外，SPARC过表达通过降低VEGFR2、ERK1/2和AKT信号通路的激活来抑制VEGF诱导的GC细胞增殖并使细胞周期停滞。SPARC通过降低MMP-７、MMP-９、N-钙黏蛋白、Sp1和p-ERK1/2的表达来抑制GC的侵袭和迁移。在体内实验中，通过尾静脉注射建立癌症转移小鼠模型。结果显示，小鼠中过表达SPARC的GC细胞的肺转移比对照细胞少得多。
