Overexpression of macrophage inflammatory protein-3α in oral cavity squamous cell carcinoma is associated with nodal metastasis

Overexpression of macrophage inflammatory protein-3α in oral cavity squamous cell carcinoma is associated with nodal metastasis
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DOI:
10.1016/j.oraloncology.2010.11.012
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发表时间:
2011-02-01
期刊:
影响因子:
4.8
通讯作者:
Yu, Jau-Song
Yu, Jau-Song
中科院分区:
医学2区
文献类型:
--
作者:
Chang, Kai-Ping;Kao, Huang-Kai;Yu, Jau-Song

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我们研究了巨噬细胞炎性蛋白(MIP)-3 α在口腔鳞状细胞癌(OSCC)中的作用,以及它是否参与调节OSCC细胞功能。研究人群包括102例OSCC患者。采用免疫组化和实时定量RT-PCR检测组织中MIP-3 α的水平。通过细胞增殖实验、跨孔迁移/侵袭实验和RNA干扰实验研究MIP-3 α对OSCC细胞功能的影响。我们发现MIP-3 α在OSCC肿瘤细胞中过表达。MIP-3 α在肿瘤细胞中的表达显著高于正常上皮细胞,如通过定量实时RT-PCR和免疫组织化学测定的。MIP-3 α的过表达与pN状态阳性显著相关(P = 0.036)。然而,没有相关性与患者的年龄,pT状态,整体病理分期,细胞分化,或周围神经浸润。根据MIP-3 α过表达的存在或不存在分层的患者亚组的长期疾病特异性生存率为70.9% vs. 54.7%(P = 0.041)。多变量分析表明MIP-3 α过表达显著降低疾病特异性生存率(风险比:2.158; P = 0.037)。此外,在体外使用特异性干扰RNA抑制OECM-1细胞中MIP-3 α表达减弱了细胞迁移和侵袭力。这些发现表明MIP-3 α在口腔鳞癌中的过度表达与患者生存的较差预后相关,并有助于肿瘤转移。(C)2010爱思唯尔有限公司版权所有。
We examined the role of macrophage inflammatory protein (MIP)-3 alpha on oral cavity squamous cell carcinoma (OSCC) and whether it was involved in modulating OSCC cell functions. The study population was comprised of 102 patients with OSCC. MIP-3 alpha levels in tissues were examined by immunohistochemistry and quantitative real-time RT-PCR. Effects of MIP-3 alpha on OSCC cell function were investigated by cell proliferation assays, trans-well migration/invasion assays, and RNA interference. We found that MIP-3 alpha was overexpressed in OSCC tumor cells. MIP-3 alpha expression was significantly higher in tumor cells vs. normal epithelial cells, as determined by both quantitative real-time RT-PCR and immunohistochemistry. Overexpression of MIP-3 alpha was significantly correlated with positive pN status (P = 0.036). Nevertheless, there were no correlations related to patient age, pT status, overall pathological stage, cell differentiation, or perineural invasion. The long-term disease-specific survival for patient subgroups stratified by the absence or presence of MIP-3 alpha overexpression was 70.9% vs. 54.7% (P = 0.041). Multivariate analysis indicated that MIP-3 alpha overexpression had a significantly lower disease-specific survival (hazard ratio: 2.158; P = 0.037). Additionally, in vitro suppression of MIP-3 alpha expression in OECM-1 cells using specific interfering RNAs attenuated cell migration and invasiveness. These findings suggest that MIP-3 alpha overexpression in OSCC is associated with a poorer prognosis for patient survival and contributes to tumor metastasis. (C) 2010 Elsevier Ltd. All rights reserved.