IL-17 expression by breast-cancer-associated macrophages: IL-17 promotes invasiveness of breast cancer cell lines.
IL-17 expression by breast-cancer-associated macrophages: IL-17 promotes invasiveness of breast cancer cell lines.
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DOI：
10.1186/bcr2195
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发表时间：
2008
期刊：
影响因子：
--
通讯作者：
Jackson AM
中科院分区：
文献类型：
--
作者：
Zhu X;Mulcahy LA;Mohammed RA;Lee AH;Franks HA;Kilpatrick L;Yilmazer A;Paish EC;Ellis IO;Patel PM;Jackson AM
IL-17在自身免疫中发挥重要作用，在多发性硬化症、类风湿性关节炎和I型糖尿病中促进自身免疫、炎症和侵袭。然而，IL-17 在癌症中的作用尚不清楚，因为很少有研究检查癌症中 IL-17 蛋白的表达。因此，我们检查了人类乳腺癌中 IL-17 蛋白的表达，并在体外模拟了其潜在的生物学意义。免疫组织化学用于测定乳腺癌中 IL-17 的表达。采用基质胶侵袭测定来检查 IL-17 对一组乳腺癌细胞系的癌细胞侵袭的影响。通过选择性拮抗剂和 MMP-2、MMP-3、MMP-9 和 MMP 组织抑制剂的免疫测定研究了基质金属蛋白酶 (MMP) 的作用。在部分患者（8/19 名患者）的瘤周区域中鉴定出具有巨噬细胞形态的表达 IL-17 的细胞。通过连续切片上的 CD68 染色来确认巨噬细胞。除偶见淋巴细胞、1例罕见多核巨细胞和1例肿瘤细胞偶见IL-17表达外，未检测到其他IL-17阳性细胞。体外向细胞系中添加 IL-17 会刺激 Matrigel 的显着侵袭。相反，IL-17不促进MCF7或T47D细胞系的侵袭。最初认为侵袭依赖于 MMP，广谱 MMP 抑制剂 GM6001 以及 MMP-2/MMP-9 和 MMP-3 的选择性拮抗剂证明了这一点。 MMP-2、MMP-3 和 MMP-9 以及 MMP 1 分泌组织抑制剂的测量未能揭示 IL-17 暴露后表达的任何变化。相反，TNF 促进 MMP 的分泌，但 IL-17 不增强 TNF，表明 IL-17 通过独立机制发挥作用。本研究首次描述了人类乳腺肿瘤中 IL-17 蛋白的原位表达，并提出 IL-17 与乳腺癌侵袭之间的直接关联。 IL-17依赖性入侵的精确效应子仍有待表征，但可能包括一系列蛋白酶，例如解整合素和金属蛋白酶蛋白或虾红素。尽管如此，这项工作确定了乳腺癌侵袭和肿瘤进展的一种新的潜在机制，其预后意义目前正在研究中。
IL-17 plays an important role in autoimmunity, promoting autoimmunity, inflammation and invasion in multiple sclerosis, rheumatoid arthritis and type I diabetes. The role of IL-17 in cancer is unclear, however, as there are few studies examining IL-17 protein expression in cancer. We therefore examined IL-17 protein expression in human breast cancer and modelled its potential biological significance in vitro. Immunohistochemistry was used to determine IL-17 expression in breast cancers. Matrigel invasion assays were employed to examine the effect of IL-17 on cancer cell invasion by a panel of breast cancer cell lines. The role of matrix metalloproteinases (MMPs) was investigated with selective antagonists and immunoassays for MMP-2, MMP-3, MMP-9 and tissue inhibitor of MMP. IL-17-expressing cells with macrophage morphology were identified in the peritumoural area of a proportion of patients (8/19 patients). Macrophages were confirmed by CD68 staining on serial sections. With the exception of occasional lymphocytes, one patient with rare multinucleate giant cells and one patient with occasional expression of IL-17 in tumour cells, no other IL-17-positive cells were detected. Addition of IL-17 to cell lines in vitro stimulated marked invasion of Matrigel. In contrast, IL-17 did not promote the invasion of MCF7 or T47D cell lines. Invasion was initially thought to be dependent on MMPs, as evidenced by the broad-spectrum MMP inhibitor GM6001 and selective antagonists of MMP-2/MMP-9 and MMP-3. Measurement of MMP-2, MMP-3 and MMP-9, and tissue inhibitor of MMP 1 secretion, failed to reveal any changes in expression following IL-17 exposure. In contrast, TNF promoted secretion of MMPs but IL-17 did not augment TNF, indicating that IL-17 acts via an independent mechanism. The present study is the first to describe in situ expression of IL-17 protein in human breast tumours and to propose a direct association between IL-17 and breast cancer invasion. The precise effectors of IL-17-dependent invasion remain to be characterised but could include a range of proteases such as a disintegrin and metalloproteinase protein or astacins. Nevertheless, this work identifies a novel potential mechanism for breast cancer invasion and tumour progression, the prognostic implication of which is currently under investigation.
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影响因子：
3.8
作者：
Chabaud, M;Garnero, P;Miossec, P
通讯作者：
Miossec, P
影响因子：
8.8
作者：
Ito, A;Nakajima, S;Sasaguri, Y;Nagase, H;Mori, Y
通讯作者：
Mori, Y
影响因子：
10.3
作者：
Hance, KW;Anderson, WF;Levine, PH
通讯作者：
Levine, PH
影响因子：
5
作者：
Bar-Eli, M
通讯作者：
Bar-Eli, M
影响因子：
20.3
作者：
Benchetrit, F;Ciree, A;Tartour, E
通讯作者：
Tartour, E