A breast cancer stem cell niche supported by juxtacrine signalling from monocytes and macrophages
Author(s)Clauser, Karl R.; Fröse, Julia; Ye, Xin; Eaton, Elinor Ng; Reinhardt, Ferenc; Donnenberg, Vera S.; Bhargava, Rohit; Carr, Steven A.; Lu, Haihui; Tam, Wai Leong; Weinberg, Robert A; ... Show more Show less
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The cell-biological program termed the epithelial-mesenchymal transition (EMT) confers on cancer cells mesenchymal traits and an ability to enter the cancer stem cell (CSC) state. However, the interactions between CSCs and their surrounding microenvironment are poorly understood. Here we show that tumour-associated monocytes and macrophages (TAMs) create a CSC niche through juxtacrine signalling with CSCs. We performed quantitative proteomic profiling and found that the EMT program upregulates the expression of CD90, also known as Thy1, and EphA4, which mediate the physical interactions of CSCs with TAMs by directly binding with their respective counter-receptors on these cells. In response, the EphA4 receptor on the carcinoma cells activates Src and NF-κ B. In turn, NF-κ B in the CSCs induces the secretion of a variety of cytokines that serve to sustain the stem cell state. Indeed, admixed macrophages enhance the CSC activities of carcinoma cells. These findings underscore the significance of TAMs as important components of the CSC niche.
DepartmentLudwig Center for Molecular Oncology; Massachusetts Institute of Technology. Department of Biology
Nature Cell Biology
Lu, Haihui et al. “A Breast Cancer Stem Cell Niche Supported by Juxtacrine Signalling from Monocytes and Macrophages.” Nature Cell Biology 16, 11 (September 2014): 1105–1117 © 2014 Macmillan Publishers Limited
Author's final manuscript