Periostin promotes immunosuppressive premetastatic niche formation to facilitate breast tumour metastasis
Periostin promotes immunosuppressive premetastatic niche formation to facilitate breast tumour metastasis
复制标题
Periostin促进免疫抑制性转移前生态位形成，促进乳腺肿瘤转移
DOI：
10.1002/path.4747
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发表时间：
2016-08-01
影响因子：
7.3
通讯作者：
Ouyang, Gaoliang
中科院分区：
文献类型：
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作者：
Wang, Zhe;Xiong, Shanshan;Ouyang, Gaoliang
骨膜蛋白（Periostin，POSTs）是一种限制播散性肿瘤细胞转移定植的因子。然而，在肿瘤转移中，POR4在调节未成熟骨髓细胞的免疫抑制功能中的作用尚未被记录。在这里，我们证明了在乳腺肿瘤转移的早期阶段，POR4促进髓源性抑制细胞（MDSC）的肺部积聚。Postn缺失减少了小鼠骨髓中的中性粒细胞和单核细胞群，并抑制了MDSC在转移前部位的积累。我们还发现，PO4缺乏的MDSC显示ERK、AKT和STAT3的活化降低，并且PO4缺乏降低了MDSC在肿瘤进展期间的免疫抑制功能。此外，POL4的促转移作用在很大程度上仅限于ER阴性乳腺癌患者。赖氨酰氧化酶有助于过氧化物酶促进的转移前小生境形成和肿瘤转移。我们的研究结果表明，POR4是必不可少的免疫抑制转移前的小生境形成在肺部乳腺肿瘤转移，是一个潜在的目标，用于预防和治疗乳腺肿瘤转移。版权所有© 2016大不列颠及爱尔兰病理学会。由John Wiley & Sons有限公司出版
Periostin (POSTN) is a limiting factor in the metastatic colonization of disseminated tumour cells. However, the role of POSTN in regulating the immunosuppressive function of immature myeloid cells in tumour metastasis has not been documented. Here, we demonstrate that POSTN promotes the pulmonary accumulation of myeloid‐derived suppressor cells (MDSCs) during the early stage of breast tumour metastasis. Postn deletion decreases neutrophil and monocytic cell populations in the bone marrow of mice and suppresses the accumulation of MDSCs to premetastatic sites. We also found that POSTN‐deficient MDSCs display reduced activation of ERK, AKT and STAT3 and that POSTN deficiency decreases the immunosuppressive functions of MDSCs during tumour progression. Moreover, the pro‐metastatic role of POSTN is largely limited to ER‐negative breast cancer patients. Lysyl oxidase contributes to POSTN‐promoted premetastatic niche formation and tumour metastasis. Our findings indicate that POSTN is essential for immunosuppressive premetastatic niche formation in the lungs during breast tumour metastasis and is a potential target for the prevention and treatment of breast tumour metastasis. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.