Open AccessSox2 Communicates with Tregs Through CCL1 to Promote the Stemness Property of Breast Cancer Cells
Author(s) -
Xu Yingxi,
Dong Xiaoli,
Qi Pingping,
Ye Yujie,
Shen Wenzhi,
Leng Liang,
Wang Lina,
Li Xuefei,
Luo Xiaohe,
Chen Yanan,
Sun Peiqing,
Xiang Rong,
Li Na
Publication year - 2017
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.2720
Subject(s) - sox2 , cancer research , biology , cancer stem cell , metastasis , breast cancer , foxp3 , population , angiogenesis , stem cell , tumor microenvironment , immunology , cancer , immune system , microbiology and biotechnology , medicine , transcription factor , biochemistry , genetics , environmental health , tumor cells , gene
As an important component of the tumor microenvironment, 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 upregulate the stemness property of breast cancer cells. Tregs increased the side‐population and the Aldehyde dehydrogenase‐bright population of mouse breast cancer cells, promoted their sphere formation in a paracrine manner, and enhanced the expression of stemness genes, such as Sox2 and so forth. In addition, Tregs increased tumorigenesis, metastasis, and chemoresistance of breast cancer cells. Furthermore, Sox2‐overexpression tumor cells activated 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. S tem C ells 2017;35:2351–2365