1. LSECtin on tumor-associated macrophages enhances breast cancer stemness via interaction with its receptor BTN3A3
- Author
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Guilin Peng, Lu Qian, Wang Xing, Zefei Jiang, Fuchu He, Ning Lu, Jianbin Li, Jun Wang, Jing Liu, Di Liu, Xiaopeng Hao, Yuandong Tao, Dianyuan Zhao, Li Tang, and Pengbo Cao
- Subjects
Antigens, Differentiation, Myelomonocytic ,Mice, Nude ,Breast Neoplasms ,Kaplan-Meier Estimate ,Biology ,Article ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Breast cancer ,Cancer stem cell ,RNA interference ,Antigens, CD ,Cell Line, Tumor ,medicine ,Gene silencing ,Animals ,Humans ,Lectins, C-Type ,RNA, Small Interfering ,Molecular Biology ,030304 developmental biology ,Cell Proliferation ,Mice, Knockout ,0303 health sciences ,Butyrophilins ,Cell growth ,Macrophages ,Cancer ,Cell Biology ,medicine.disease ,Juxtacrine signalling ,Research Highlight ,Mice, Inbred C57BL ,Cancer research ,Neoplastic Stem Cells ,Female ,RNA Interference ,Signal transduction ,030217 neurology & neurosurgery ,Protein Binding ,Signal Transduction - Abstract
Macrophages have been suggested to contribute to constructing a cancer stem cell (CSC) niche. However, whether and how macrophages regulate the activity of CSCs through juxtacrine signaling are poorly understood. Here we report LSECtin, a transmembrane protein highly expressed on tumor-associated macrophages (TAMs), enhances stemness of breast cancer cells (BCCs). We identified BTN3A3, a B7 family member with previously unknown functions as the receptor for LSECtin on BCCs responsible for stemness-promoting effect of LSECtin. In mice bearing human tumor xenografts, either macrophage-specific ablation of LSECtin or silencing of BTN3A3 in BCCs decreased CSC frequency and tumor growth. Admixture of LSECtin-positive macrophages increased the tumorigenic activity of BCCs dependent on BTN3A3. Disruption of the LSECtin-BTN3A3 axis with BTN3A3-Fc or anti-BTN3A3 mAb has a therapeutic effect on breast cancer. These findings define a juxtacrine signaling mechanism by which TAMs promote cancer stemness. Targeting this axis in the CSC niche may provide potential therapies to breast cancer.
- Published
- 2018