3 years ago

Sox2 Communicates With Tregs Through CCL1 To Promote The Stemness Property Of Breast Cancer Cells

Sox2 Communicates With Tregs Through CCL1 To Promote The Stemness Property Of Breast Cancer Cells
Na Li, Rong Xiang, Peiqing Sun, Xuefei Li, Yingxi Xu, Xiaohe Luo, Yujie Ye, Lina Wang, Xiaoli Dong, Wenzhi Shen, Pingping Qi, Yanan Chen, Liang Leng
As an important component of tumor microenvrionment, CD4+CD25+ Tregs reduce antitumor immunity, promote angiogenesis and metastasis in breast cancer. However, their function in regulating the "stemness" of tumor cells and the communication between Tregs and cancer stem cells (CSCs) remain elusive. Here, we disclose that the primarily cultured Tregs isolated from breast-tumor-bearing Foxp3-EGFP mouse up-regulate the stemness property of breast cancer cells. Tregs increased the side-population and the ALDHbr population of mouse breast cancer cells, promoted their sphere formation in a paracrine manner and enhanced the expression of stemness genes, such as Sox2 etc. In addition, Tregs increased tumorigenesis, metastasis and chemoresistance of breast cancer cells. Furthermore, Sox2-overexpression tumor cells acitivated NF-κB-CCL1 signaling to recruit Tregs through reducing the binding of H3K27Me3 on promoter regions of p65 and Ccl1. These findings reveal the functional interaction between Tregs and CSCs and indicate that targeting on the communication between them is a promising strategy in breast cancer therapy. This article is protected by copyright. All rights reserved. Schematic summary of our proposed model: Tregs enhance the stemness of breast cancer cells, as reflected by the increasement in the side population, ALDHbr cell population, sphere-formaton ability, tumor initiation ability, metastasis and chemoresistance properties. Reciprocally, the CSCs recruit Tregs through Sox2-NFκB-CCL1 signaling.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/stem.2720

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