IL17 Promotes Mammary Tumor Progression by Changing the Behavior of Tumor Cells and Eliciting Tumorigenic Neutrophils Recruitment.
IL17 Promotes Mammary Tumor Progression by Changing the Behavior of Tumor Cells and Eliciting Tumorigenic Neutrophils Recruitment.
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DOI：
10.1158/0008-5472.can-15-0054
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发表时间：
2015-09-15
期刊：
影响因子：
11.2
通讯作者：
Silva JS
中科院分区：
文献类型：
--
作者：
Benevides L;da Fonseca DM;Donate PB;Tiezzi DG;De Carvalho DD;de Andrade JM;Martins GA;Silva JS
乳腺浸润性导管癌（IDC）的侵袭性与il - 17水平升高有关。研究il - 17在侵袭性乳腺肿瘤发病中的作用，我们发现转移性原发肿瘤浸润T淋巴细胞产生il - 17水平升高，而il - 17中和抑制肿瘤生长，阻止中性粒细胞和肿瘤细胞向继发性疾病部位迁移。致瘤性中性粒细胞促进疾病进展，产生CXCL1、MMP9、VEGF和TNFα，它们的消耗抑制肿瘤生长。IL17A还能诱导转移性肿瘤细胞产生IL6和CCL20，有利于Th17的募集和分化。此外，IL17A改变了非转移性肿瘤细胞的基因表达谱和行为，在体内引起肿瘤生长，证实了IL17在肿瘤中的作用。此外，高il - 17表达与IDC患者较低的无病生存率和较差的预后相关。因此，il - 17阻断是控制浸润性乳腺肿瘤的一种有吸引力的方法。
The aggressiveness of invasive ductal carcinoma (IDC) of the breast is associated with increased IL17 levels. Studying the role of IL17 in invasive breast tumor pathogenesis, we found that metastatic primary tumor-infiltrating T lymphocytes produced elevated levels of IL17, whereas IL17 neutralization inhibited tumor growth and prevented the migration of neutrophils and tumor cells to secondary disease sites. Tumorigenic neutrophils promote disease progression, producing CXCL1, MMP9, VEGF, and TNFα, and their depletion suppressed tumor growth. IL17A also induced IL6 and CCL20 production in metastatic tumor cells, favoring the recruitment and differentiation of Th17. In addition, IL17A changed the gene-expression profile and the behavior of nonmetastatic tumor cells, causing tumor growth in vivo, confirming the protumor role of IL17. Furthermore, high IL17 expression was associated with lower disease-free survival and worse prognosis in IDC patients. Thus, IL17 blockade represents an attractive approach for the control of invasive breast tumors.