A breast cancer stem cell niche supported by juxtacrine signalling from monocytes and macrophages.

Nat Cell Biol
Authors
Keywords
Abstract

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-κB. In turn, NF-κB 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.

Year of Publication
2014
Journal
Nat Cell Biol
Volume
16
Issue
11
Pages
1105-17
Date Published
2014 Nov
ISSN
1476-4679
URL
DOI
10.1038/ncb3041
PubMed ID
25266422
PubMed Central ID
PMC4296514
Links
Grant list
R01-CA078461 / CA / NCI NIH HHS / United States
U24 CA160034 / CA / NCI NIH HHS / United States
P01 CA080111 / CA / NCI NIH HHS / United States
P30 CA047904 / CA / NCI NIH HHS / United States
P30 CA014051 / CA / NCI NIH HHS / United States
P30CA047904 / CA / NCI NIH HHS / United States
U54 CA163109 / CA / NCI NIH HHS / United States
P01-CA080111 / CA / NCI NIH HHS / United States
R01 CA078461 / CA / NCI NIH HHS / United States
U24CA160034 / CA / NCI NIH HHS / United States
U54-CA163109 / CA / NCI NIH HHS / United States