Macrophage migration inhibitory factor - a therapeutic target in gallbladder cancer.
Macrophage migration inhibitory factor - a therapeutic target in gallbladder cancer.
复制标题
DOI：
10.1186/s12885-015-1855-z
复制
发表时间：
2015-11-04
期刊：
影响因子：
3.8
通讯作者：
Chatterjee A
中科院分区：
文献类型：
--
作者：
Subbannayya T;Leal-Rojas P;Barbhuiya MA;Raja R;Renuse S;Sathe G;Pinto SM;Syed N;Nanjappa V;Patil AH;Garcia P;Sahasrabuddhe NA;Nair B;Guerrero-Preston R;Navani S;Tiwari PK;Santosh V;Sidransky D;Prasad TS;Gowda H;Roa JC;Pandey A;Chatterjee A
胆囊癌的预后不良是由于疾病出现较晚、缺乏可靠的早期诊断生物标志物以及有限的靶向治疗。早期诊断标志物和新的治疗靶点可以显着改善胆囊癌的临床管理。使用同量异序标签进行基于相对和绝对定量标记的定量蛋白质组学方法，对四种基于侵袭性（非侵袭性到高度侵袭性）的胆囊癌细胞系进行蛋白质组学分析。采用免疫组织化学方法分析胆囊腺癌组织中巨噬细胞迁移抑制因子的表达。使用 MIF 抑制剂、ISO-1 和 4-IPP 或其特异性 siRNA 在一组胆囊癌细胞系中进行体外细胞测定。定量蛋白质组学实验鉴定出 3,653 种蛋白质，其中与非侵袭性细胞系 TGBC24TKB 相比，在侵袭性细胞系（OCUG-1、NOZ 和 GB-d1）中发现 654 种蛋白过表达，387 种蛋白下调。其中，观察到巨噬细胞迁移抑制因子（MIF）在两种侵袭细胞系中高度过表达。 MIF 是一种多效性促炎细胞因子，在包括癌症在内的多种疾病中发挥致病作用。据报道，MIF 在多种癌症的肿瘤细胞增殖和侵袭中发挥着核心作用。对肿瘤组织微阵列进行 MIF 表达的免疫组织化学标记显示，在 29 例胆囊腺癌病例中，有 21 例 MIF 过度表达。使用siRNA和/或MIF拮抗剂沉默/抑制MIF导致胆囊癌细胞的细胞活力、集落形成能力和侵袭特性显着降低。我们的研究结果支持 MIF 在肿瘤侵袭性中的作用，并表明其作为胆囊癌治疗靶点的潜在应用。本文的在线版本 (doi:10.1186/s12885-015-1855-z) 包含补充材料，可供授权用户使用。
Poor prognosis in gallbladder cancer is due to late presentation of the disease, lack of reliable biomarkers for early diagnosis and limited targeted therapies. Early diagnostic markers and novel therapeutic targets can significantly improve clinical management of gallbladder cancer. Proteomic analysis of four gallbladder cancer cell lines based on the invasive property (non-invasive to highly invasive) was carried out using the isobaric tags for relative and absolute quantitation labeling-based quantitative proteomic approach. The expression of macrophage migration inhibitory factor was analysed in gallbladder adenocarcinoma tissues using immunohistochemistry. In vitro cellular assays were carried out in a panel of gallbladder cancer cell lines using MIF inhibitors, ISO-1 and 4-IPP or its specific siRNA. The quantitative proteomic experiment led to the identification of 3,653 proteins, among which 654 were found to be overexpressed and 387 were downregulated in the invasive cell lines (OCUG-1, NOZ and GB-d1) compared to the non-invasive cell line, TGBC24TKB. Among these, macrophage migration inhibitory factor (MIF) was observed to be highly overexpressed in two of the invasive cell lines. MIF is a pleiotropic proinflammatory cytokine that plays a causative role in multiple diseases, including cancer. MIF has been reported to play a central role in tumor cell proliferation and invasion in several cancers. Immunohistochemical labeling of tumor tissue microarrays for MIF expression revealed that it was overexpressed in 21 of 29 gallbladder adenocarcinoma cases. Silencing/inhibition of MIF using siRNA and/or MIF antagonists resulted in a significant decrease in cell viability, colony forming ability and invasive property of the gallbladder cancer cells. Our findings support the role of MIF in tumor aggressiveness and suggest its potential application as a therapeutic target for gallbladder cancer. The online version of this article (doi:10.1186/s12885-015-1855-z) contains supplementary material, which is available to authorized users.