Expression of Forkhead box P3 in tumour cells causes immunoregulatory function of signet ring cell carcinoma of the stomach.
Expression of Forkhead box P3 in tumour cells causes immunoregulatory function of signet ring cell carcinoma of the stomach.
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DOI：
10.1038/bjc.2012.141
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发表时间：
2012-05-08
影响因子：
8.8
通讯作者：
Hirakawa, K.
中科院分区：
文献类型：
--
作者：
Yoshii, M.;Tanaka, H.;Ohira, M.;Muguruma, K.;Iwauchi, T.;Lee, T.;Sakurai, K.;Kubo, N.;Yashiro, M.;Sawada, T.;Hirakawa, K.
最近有报道称，转录因子叉头盒P3 （FoxP3）不仅在调节性T细胞（Tregs）中表达，而且在癌细胞中也表达。本研究旨在阐明FoxP3在胃癌中表达的临床意义。我们对2000年至2010年194例接受手术切除的胃癌患者进行FoxP3免疫组化染色，检测FoxP3表达与临床病理特征的关系。我们还利用胃癌细胞系研究了FoxP3的免疫抑制功能。免疫组化染色显示foxp3阳性细胞存在于肿瘤组织中，包括Tregs和肿瘤细胞。在79.3%的印戒细胞癌患者中可见叉头盒p3阳性肿瘤细胞，FoxP3的表达与淋巴结转移有显著相关性。我们发现转化生长因子-β增强了印戒细胞癌细胞系中FoxP3 mRNA的表达。吲哚胺-2,3-双加氧酶和半乳糖凝集素-1是treg介导的免疫抑制的关键效应物，FoxP3敲低后下调。提示肿瘤细胞表达FoxP3可能在胃癌的免疫逃逸中起重要作用，并与剑鞘性胃癌的恶性潜能有关。
It was recently reported that the transcription factor Forkhead box P3 (FoxP3) is expressed not only in regulatory T cells (Tregs) but also in cancer cells. The aim of this study was to clarify the clinical significance of FoxP3 expression in gastric carcinoma. We performed immunohistochemical staining of FoxP3 to examine the association of FoxP3 expression with clinicopathological features of 194 patients with gastric cancer who underwent surgical resection from 2000 to 2010. We also investigated the immunosuppressive function of FoxP3 using gastric cancer cell lines. Immunohistochemical staining indicated FoxP3-positive cells within tumour tissue including both Tregs and tumour cells. Forkhead box P3-positive tumour cells were observed in 79.3% of signet ring cell carcinoma patients, and the expression of FoxP3 showed a significant correlation with lymph node metastasis. We showed that transforming growth factor-β augmented FoxP3 mRNA expression in cell lines derived from signet ring cell carcinoma. Indoleamine-2,3-dioxygenase and galectin-1, key effectors of Treg-mediated immunosuppression, were downregulated by FoxP3 knockdown. Our findings suggested that FoxP3 expression by tumour cells might have important roles in immune escape of gastric carcinoma, and be associated with the malignant potential of scirrhous gastric carcinoma.
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影响因子：
9.2
作者：
Shu, Suyu;Cochran, Alistair J.;Maecker, Holden T.
通讯作者：
Maecker, Holden T.
影响因子：
8.8
作者：
Ino, K;Yoshida, N;Kajiyama, H;Shibata, K;Yamamoto, E;Kidokoro, K;Takahashi, N;Terauchi, M;Nawa, A;Nomura, S;Nagasaka, T;Takikawa, O;Kikkawa, F
通讯作者：
Kikkawa, F
影响因子：
8.8
作者：
Mizukami, Y.;Kono, K.;Kawaguchi, Y.;Akaike, H.;Kamimura, K.;Sugai, H.;Fujii, H.
通讯作者：
Fujii, H.
影响因子：
3.8
作者：
Mansfield AS;Heikkila PS;Vaara AT;von Smitten KA;Vakkila JM;Leidenius MH
通讯作者：
Leidenius MH
影响因子：
8.8
作者：
Polak, M. E.;Borthwick, N. J.;Gabriel, F. G.;Johnson, P.;Higgins, B.;Hurren, J.;McCormick, D.;Jager, M. J.;Cree, I. A.
通讯作者：
Cree, I. A.