Periostin promotes immunosuppressive premetastatic niche formation to facilitate breast tumour metastasis

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• 作者：Zhe Wang ; Shanshan Xiong ; Yubin Mao ; Mimi Chen ; Xiaohong Ma ; Xueliang Zhou ; Zhenling Ma ; Fan Liu ; Zhengjie Huang ; Qi Luo and Gaoliang Ouyang
• 刊名：The Journal of Pathology
• 出版年：2016
• 出版时间：August 2016
• 年：2016
• 卷：239
• 期：4
• 页码：484-495
• 全文大小：8264K
• ISSN：1096-9896

文摘

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