Stromal Macrophage Expressing CD204 is Associated with Tumor Aggressiveness in Lung Adenocarcinoma
Stromal Macrophage Expressing CD204 is Associated with Tumor Aggressiveness in Lung Adenocarcinoma
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DOI：
10.1097/jto.0b013e3181eba692
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发表时间：
2010-10-01
影响因子：
20.4
通讯作者：
Ochiai, Atsushi
中科院分区：
文献类型：
--
作者：
Ohtaki, Yoichi;Ishii, Genichiro;Ochiai, Atsushi
背景资料：肿瘤组织由可变数量的癌细胞和基质细胞组成，并且肿瘤相关巨噬细胞被募集到癌症诱导的基质中并产生特定的微环境。或者，活化的巨噬细胞已知CD 204（M2表型）与肿瘤进展和结果相关，并且已经报道CD 204在一些肿瘤中的M2巨噬细胞中表达。为了研究CD 204阳性巨噬细胞是否反映肺腺癌的肿瘤侵袭性，我们研究了CD 204-阳性间质巨噬细胞和临床病理特征和结果在170例连续切除病例。我们还研究了CD 204阳性巨噬细胞的数量与参与M2巨噬细胞迁移和分化的细胞因子表达水平之间的关系。对数秩检验显示，CD 204阳性巨噬细胞数量与不良预后显著相关（p = 0.0073），而表达CD 68（一种泛巨噬细胞/单核细胞标志物）的巨噬细胞数量具有边际预后意义（p = 0.0789）。我们评估了细胞因子IL-6、IL-10、IL-12 a、IL-12 b、M-集落刺激因子、IFN-γ、单核细胞趋化蛋白-1和CD 204阳性巨噬细胞数。参与M2巨噬细胞分化、聚集和迁移的IL-10和单核细胞趋化蛋白-1的表达水平与CD 204阳性巨噬细胞的数量显著相关（分别为p = 0.031和p = 0.031）。这些发现表明，CD 204阳性巨噬细胞清楚地反映了肺腺癌中肿瘤相关巨噬细胞的肿瘤促进表型。
Background: Tumor tissue is composed of variable numbers of cancer cells and stromal cells, and tumor-associated macrophages are recruited into cancer-induced stroma and produce a specific microenvironment. Alternatively, activated macrophages (M2 phenotype) are known to be related to tumor progression and outcome, and CD204 has been reported to be expressed in M2 macrophages in some tumors.Methods: To investigate whether CD204-positive macrophages reflect tumor aggressiveness in adenocarcinoma of the lung, we investigated the relationships between the numbers of CD204-positive stromal macrophages and both clinicopathological features and outcome in 170 consecutive resected cases. We also examined the relationships between the numbers of CD204-positive macrophages and the expression levels of cytokines involved in the migration and differentiation of M2 macrophages.Results: The numbers of CD204-positive macrophages were significantly correlated with several prognostic factors. The log-rank test showed a significant association between the numbers of CD204-positive macrophages and a poor outcome (p = 0.0073), whereas the numbers of macrophages expressing CD68, a pan-macrophage/monocyte marker, were of marginal prognostic significance (p = 0.0789). We evaluated associations between the levels of expression of the cytokines IL-6, IL-10, IL-12a, IL-12b, M-colony-stimulating factor, IFN-gamma-., and monocyte chemoattractant protein-1 in cancer tissue and the numbers of CD204-positive macrophages. The expression levels of IL-10 and monocyte chemoattractant protein-1, which are involved in differentiation, accumulation, and migration of M2 macrophages, were significantly correlated with the numbers of CD204-positive macrophages ( p = 0.031 and p = 0.031, respectively).Conclusion: These findings demonstrated that CD204-positive macrophages clearly reflect the tumor-promoting phenotype of tumor-associated macrophages in lung adenocarcinoma.