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Cancer-associated fibroblast-secreted CXCL16 attracts monocytes to promote stroma activation in triple-negative breast cancers

Allaoui, Roni LU ; Bergenfelz, Caroline LU ; Mohlin, Sofie LU ; Hagerling, Catharina LU ; Salari, Kiarash; Werb, Zena; Anderson, Robin L.; Ethier, Stephen P.; Jirström, Karin LU and Påhlman, Sven LU , et al. (2016) In Nature Communications 7.
Abstract

Triple-negative (TN) breast cancers (ER â ' PR â ' HER2 â ') are highly metastatic and associated with poor prognosis. Within this subtype, invasive, stroma-rich tumours with infiltration of inflammatory cells are even more aggressive. The effect of myeloid cells on reactive stroma formation in TN breast cancer is largely unknown. Here, we show that primary human monocytes have a survival advantage, proliferate in vivo and develop into immunosuppressive myeloid cells expressing the myeloid-derived suppressor cell marker S100A9 only in a TN breast cancer environment. This results in activation of cancer-associated fibroblasts and expression of CXCL16, which we show to be a monocyte chemoattractant. We propose that this migratory feedback... (More)

Triple-negative (TN) breast cancers (ER â ' PR â ' HER2 â ') are highly metastatic and associated with poor prognosis. Within this subtype, invasive, stroma-rich tumours with infiltration of inflammatory cells are even more aggressive. The effect of myeloid cells on reactive stroma formation in TN breast cancer is largely unknown. Here, we show that primary human monocytes have a survival advantage, proliferate in vivo and develop into immunosuppressive myeloid cells expressing the myeloid-derived suppressor cell marker S100A9 only in a TN breast cancer environment. This results in activation of cancer-associated fibroblasts and expression of CXCL16, which we show to be a monocyte chemoattractant. We propose that this migratory feedback loop amplifies the formation of a reactive stroma, contributing to the aggressive phenotype of TN breast tumours. These insights could help select more suitable therapies targeting the stromal component of these tumours, and could aid prediction of drug resistance.

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Nature Communications
volume
7
publisher
Nature Publishing Group
external identifiers
  • scopus:84991394206
  • wos:000385550000001
ISSN
2041-1723
DOI
10.1038/ncomms13050
language
English
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yes
id
8e9ebc42-f85b-4ced-995a-ae674f8a0a2a
date added to LUP
2016-10-31 11:17:20
date last changed
2017-11-12 04:25:38
@article{8e9ebc42-f85b-4ced-995a-ae674f8a0a2a,
  abstract     = {<p>Triple-negative (TN) breast cancers (ER â ' PR â ' HER2 â ') are highly metastatic and associated with poor prognosis. Within this subtype, invasive, stroma-rich tumours with infiltration of inflammatory cells are even more aggressive. The effect of myeloid cells on reactive stroma formation in TN breast cancer is largely unknown. Here, we show that primary human monocytes have a survival advantage, proliferate in vivo and develop into immunosuppressive myeloid cells expressing the myeloid-derived suppressor cell marker S100A9 only in a TN breast cancer environment. This results in activation of cancer-associated fibroblasts and expression of CXCL16, which we show to be a monocyte chemoattractant. We propose that this migratory feedback loop amplifies the formation of a reactive stroma, contributing to the aggressive phenotype of TN breast tumours. These insights could help select more suitable therapies targeting the stromal component of these tumours, and could aid prediction of drug resistance.</p>},
  articleno    = {13050},
  author       = {Allaoui, Roni and Bergenfelz, Caroline and Mohlin, Sofie and Hagerling, Catharina and Salari, Kiarash and Werb, Zena and Anderson, Robin L. and Ethier, Stephen P. and Jirström, Karin and Påhlman, Sven and Bexell, Daniel and Tahin, Balázs and Johansson, Martin E. and Larsson, Christer and Leandersson, Karin},
  issn         = {2041-1723},
  language     = {eng},
  month        = {10},
  publisher    = {Nature Publishing Group},
  series       = {Nature Communications},
  title        = {Cancer-associated fibroblast-secreted CXCL16 attracts monocytes to promote stroma activation in triple-negative breast cancers},
  url          = {http://dx.doi.org/10.1038/ncomms13050},
  volume       = {7},
  year         = {2016},
}