ADAMTS5 acts as a tumor suppressor by inhibiting migration, invasion and angiogenesis in human gastric cancer
ADAMTS5 acts as a tumor suppressor by inhibiting migration, invasion and angiogenesis in human gastric cancer
复制标题
ADAMTS5 通过抑制人胃癌的迁移、侵袭和血管生成来充当肿瘤抑制剂
DOI：
10.1007/s10120-018-0866-2
复制
发表时间：
2019-03-01
期刊：
影响因子：
7.4
通讯作者：
Yang, Zuli
中科院分区：
文献类型：
--
作者：
Huang, Jintuan;Sun, Yi;Yang, Zuli
背景据报道ADAMTS5 参与了多种人类肿瘤的进展。然而，ADAMTS5在胃癌（GC）中的作用仍不清楚。方法通过实时定量PCR（qRT-PCR）和免疫组织化学（IHC）分析GC细胞系和组织中ADAMTS5的表达水平，并检查ADAMTS5表达与临床病理特征和生存之间的相关性。采用Transwell实验、伤口愈合实验和细胞粘附实验等体外实验进一步探讨ADAMTS5的生物学功能。 MAP 激酶通路微阵列用于识别潜在机制。还使用 IHC 分析 ADAMTS5 和 ETS1 的表达以及微血管密度 (MVD)，以确定与 GC 中血管生成的相关性。结果 ADAMTS5 表达在胃癌组织中下调。 ADAMTS5低表达与性别、组织学类型、分化程度、M分期、TNM分期及血管侵犯相关，也是GC患者预后不良的独立指标。 ADAMTS5 过表达显着抑制 GC 细胞迁移和侵袭，并增强细胞与细胞外基质 (ECM) 的粘附，而 ADAMTS5 敲低则产生相反的效果。此外，ADAMTS5的表达状态与ETS1表达和MVD呈负相关。结论ADAMTS5在GC中下调，并通过抑制ETS1介导的MVD变化来抑制肿瘤转移和血管生成，并可能作为人类GC中的新型预后标志物和潜在治疗靶点。
BackgroundADAMTS5 has been reported to be involved in the progression of several human tumors. Nevertheless, the role of ADAMTS5 in gastric cancer (GC) remains poorly defined.MethodsADAMTS5 expression levels were analyzed by quantitative real-time PCR (qRT-PCR) and immunohistochemistry (IHC) in GC cell lines and tissues, and the correlations between ADAMTS5 expression and clinicopathological features and survival were also examined. In vitro assays, including transwell assays, wound healing assays and cell adhesion assays, were employed to further explore the biological functions of ADAMTS5. A MAP kinase pathway microarray was used to identify the underlying mechanisms. The expression of ADAMTS5 and ETS1 and the microvessel density (MVD) were also analyzed using IHC to determine correlations with angiogenesis in GC.ResultsADAMTS5 expression was downregulated in gastric cancer tissues. Low expression of ADAMTS5 was associated with gender, histological type, degree of differentiation, M stage, TNM stage and vascular invasion, and was also an independent indicator of a poor prognosis for patients with GC. ADAMTS5 overexpression markedly inhibited GC cell migration and invasion and enhanced cell adhesion to the extracellular matrix (ECM), whereas knockdown of ADAMTS5 exerted the opposite effects. Furthermore, the ADAMTS5 expression status was negatively correlated with ETS1 expression and MVD.ConclusionADAMTS5 is downregulated in GC and suppresses tumor metastasis and angiogenesis by inhibiting ETS1-mediated changes in MVD and potentially acts as a novel prognostic marker and a potential therapeutic target in human GC.