TREM-1 is induced in tumor associated macrophages by cyclo-oxygenase pathway in human non-small cell lung cancer.

TREM-1 is induced in tumor associated macrophages by cyclo-oxygenase pathway in human non-small cell lung cancer.
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DOI:
10.1371/journal.pone.0094241
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
Sadikot RT
Sadikot RT
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Yuan Z;Mehta HJ;Mohammed K;Nasreen N;Roman R;Brantly M;Sadikot RT

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人们越来越认识到肿瘤微环境在肺癌的发生和发展中起着关键作用。特别地,已经显示肿瘤微环境中癌细胞、巨噬细胞和炎症反应的相互作用促进癌细胞侵袭和转移。巨噬细胞中免疫编辑肿瘤生长的特定分子途径尚未明确。髓样细胞上表达的触发受体1(TREM-1)是在选定的髓样细胞(主要是单核细胞/巨噬细胞)上表达的超级免疫球蛋白家族的成员。最近的研究表明,TREM-1在肿瘤中的表达可以预测肝癌和肺癌中的癌症侵袭性和疾病结果,然而TREM-1在癌症背景下的表达机制尚未确定。在这项研究中,我们证明了来自非小细胞肺癌患者的肿瘤组织显示TREM-1和PGE 2的表达增加。免疫组化和免疫荧光证实TREM-1的表达选择性地见于CD 68阳性的巨噬细胞。通过采用体外模型,我们证实了TREM-1的表达在与人肺癌细胞共培养的巨噬细胞中增加。用考克斯-2抑制剂和si考克斯-2的研究表明,肿瘤微环境中巨噬细胞中TREM-1的表达依赖于考克斯-2信号传导。这些研究首次确定了肿瘤微环境中巨噬细胞中肿瘤考克斯-2诱导、PGE 2产生和TREM-1表达之间的联系,并提示TREM-1可能是肿瘤免疫调节的新靶点。
It is increasingly recognized that the tumor microenvironment plays a critical role in the initiation and progression of lung cancer. In particular interaction of cancer cells, macrophages, and inflammatory response in the tumor microenvironment has been shown to facilitate cancer cell invasion and metastasis. The specific molecular pathways in macrophages that immunoedit tumor growth are not well defined. Triggering receptor expressed on myeloid cells 1 (TREM-1) is a member of the super immunoglobulin family expressed on a select group of myeloid cells mainly monocyte/macrophages. Recent studies suggest that expression of TREM-1 in tumors may predict cancer aggressiveness and disease outcomes in liver and lung cancer however the mechanism of TREM-1 expression in the setting of cancer is not defined. In this study we demonstrate that tumor tissue from patients with non-small cell lung cancer show an increased expression of TREM-1 and PGE2. Immunohistochemistry and immunofluorescence confirmed that the expression of TREM-1 was selectively seen in CD68 positive macrophages. By employing an in vitro model we confirmed that expression of TREM-1 is increased in macrophages that are co-cultured with human lung cancer cells. Studies with COX-2 inhibitors and siCOX-2 showed that expression of TREM-1 in macrophages in tumor microenvironment is dependent on COX-2 signaling. These studies for the first time define a link between tumor COX-2 induction, PGE2 production and expression of TREM-1 in macrophages in tumor microenvironment and suggest that TREM-1 might be a novel target for tumor immunomodulation.
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