期刊
INTERNATIONAL JOURNAL OF CANCER
卷 140, 期 6, 页码 1370-1383出版社
WILEY
DOI: 10.1002/ijc.30538
关键词
mo-MDSCs; premetastatic niche; E-selectin; IL-1 beta; tumor cell arrest
类别
资金
- National Nature Science Foundation of China [81372288, 81172014, 81670095]
- Natural Science Foundation of Jilin Province [20150101186JC]
The tumor premetastatic niche initiated by primary tumors is constructed by multiple molecular factors and cellular components and provides permissive condition that allows circulating tumor cells to successfully metastasize. Myeloid-derived suppressor cells (MDSCs), a population of immature cells in pathological conditions, play a critical role in the formation of the premetastatic niche. However, few researches are focused on the function of monocytic MDSCs (mo-MDSCs), a subtype of MDSCs, in the construction of the niche. Here, we show that the number of mo-MDSCs is significantly increased in the premetastatic lungs of tumor-bearing mice, thus promoting tumor cell arrest and metastasis. Before the arrival of tumor cells, the lung-recruited mo-MDSCs produced IL-1 beta, thereby increasing E-selectin expression and promoting tumor cell arrest on endothelial cells. Depletion of mo-MDSCs in the premetastatic lungs decreased IL-1 beta production, resulting in reduced E-selectin expression. In addition, compared with alveolar macrophages and interstitial macrophages, mo-MDSCs were the major source of IL-1 beta expression in the premetastatic lungs. Cytokine array analyses and transwell experiments revealed that CCL12 recruits mo-MDSCs to premetastatic lungs. CCL12 knockdown in tumor-bearing mice significantly decreased mo-MDSC infiltration into the premetastatic lungs, leading to reduced E-selectin expression. Overall, the permissive conditions produced by the infiltrated mo-MDSCs correlated with increased tumor cell arrest and metastasis. These results reveal a novel role of mo-MDSCs in constructing the premetastatic niche. Thus, inhibition of mo-MDSCs infiltration may change the premetastatic niche to normal condition and attenuate tumor metastasis.
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