Follicular thyroid carcinoma but not adenoma recruits tumor-associated macrophages by releasing CCL15.
Follicular thyroid carcinoma but not adenoma recruits tumor-associated macrophages by releasing CCL15.
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滤泡性甲状腺癌（而非腺瘤）通过释放 CCL15 来招募肿瘤相关巨噬细胞。
DOI：
10.1186/s12885-016-2114-7
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发表时间：
2016-02-15
期刊：
影响因子：
3.8
通讯作者：
Ning G
中科院分区：
文献类型：
--
作者：
Huang FJ;Zhou XY;Ye L;Fei XC;Wang S;Wang W;Ning G
滤泡性甲状腺癌(FTC)和滤泡性腺瘤(FA)的术前鉴别诊断是临床上的一个挑战。人们已经做了很多努力，但大多数集中在肿瘤细胞上，而肿瘤相关巨噬细胞(TAMs)在FTC中的作用尚不清楚。这里我们分析了FTC和FA中的TAMS的区别。我们首先通过CD68免疫组织化学染色分析了59例经组织学证实的FTC和47例FAs中TAMs的密度。用抗体芯片检测FTC和FA产生的细胞因子，并用定量聚合酶链式反应进行验证。用含和不含抗CCL15中和抗体的FTC细胞株FTC133和WRO82-1的条件培养液诱导单核细胞THP-1趋化。最后，用免疫组织化学方法检测FTC和FA中CCL15蛋白的表达。FTC组CD6 8+细胞平均密度为9.5 ± 5.4个/野，显著高于FA组(4.9 ± 3.4个/野，p <； 0.001)。随后的图谱显示，与FA相比，CCL15是FTC中含量最丰富的趋化因子。FTC组CCL15mRNA是FA组的51.4倍。Cm诱导THP-1细胞趋化33 ~ 77%，抗CCL15中和抗体以剂量依赖方式抑制THP-1细胞迁移。此外，我们在67.8%的FTC中观察到CCL15免疫阳性染色，而在FA中则为23.4%。我们的研究表明，FTC可能通过产生CCL15来诱导TAMS的渗透。甲状腺滤泡性病变中TAMS和CCL15的检测可用于临床鉴别FTC和FA术前诊断。本文的在线版本(doi：10.1186/s12885-0162114-7)包含补充材料，授权用户可以使用。
The differential diagnosis of follicular thyroid carcinoma (FTC) and follicular adenoma (FA) before surgery is a clinical challenge. Many efforts have been made but most focusing on tumor cells, while the roles of tumor associated macrophages (TAMs) remained unclear in FTC. Here we analyzed the differences between TAMs in FTC and those in FA. We first analyzed the density of TAMs by CD68 immunostaining in 59 histologically confirmed FTCs and 47 FAs. Cytokines produced by FTC and FA were profiled using antibody array, and validated by quantitative PCR. Chemotaxis of monocyte THP-1 was induced by condition medium of FTC cell lines (FTC133 and WRO82-1) with and without anti-CCL15 neutralizing antibody. Finally, we analyzed CCL15 protein level in FTC and FA by immunohistochemistry. The average density of CD68+ cells was 9.5 ± 5.4/field in FTC, significantly higher than that in FA (4.9 ± 3.4/field, p < 0.001). Subsequently profiling showed that CCL15 was the most abundant chemokine in FTC compared with FA. CCL15 mRNA in FTC was 51.4-folds of that in FA. CM of FTC cell lines induced THP-1 cell chemotaxis by 33 ~ 77 %, and anti-CCL15 neutralizing antibody reduced THP-1 cell migration in a dose-dependent manner. Moreover, we observed positive CCL15 immunostaining in 67.8 % of FTCs compared with 23.4 % of FAs. Our study suggested FTC might induce TAMs infiltration by producing CCL15. Measurement of TAMs and CCL15 in follicular thyroid lesions may be applied clinically to differentiate FTC from FA pre-operation. The online version of this article (doi:10.1186/s12885-016-2114-7) contains supplementary material, which is available to authorized users.