2. Academic Validation
  3. Cancer-associated fibroblast-secreted CXCL16 attracts monocytes to promote stroma activation in triple-negative breast cancers

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

  • Nat Commun. 2016 Oct 11;7:13050. doi: 10.1038/ncomms13050.
Roni Allaoui 1,  Caroline Bergenfelz 1,  Sofie Mohlin 2,  Catharina Hagerling 1 3,  Kiarash Salari 3,  Zena Werb 3,  Robin L Anderson 4,  Stephen P Ethier 5,  Karin Jirström 6,  Sven Påhlman 2,  Daniel Bexell 2,  Balázs Tahin 7,  Martin E Johansson 1 7,  Christer Larsson 2,  Karin Leandersson 1
Affiliations

Affiliations

  • 1 Department of Translational Medicine, Cancer Immunology, Lund University, Malmö 205 02, Sweden.
  • 2 Department of Laboratory Medicine, Translational Cancer Research, Lund University, Lund 223 63, Sweden.
  • 3 Department of Anatomy and the Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California 94143-0452, USA.
  • 4 Sir Peter MacCallum Department of Oncology, Peter MacCallum Cancer Centre, The University of Melbourne, Melbourne 8006, Australia.
  • 5 Department of Pathology and Laboratory Medicine, Hollings Cancer Center, Medical University of South Carolina, Charleston, South Carolina 29425, USA.
  • 6 Department of Clinical Sciences Lund, Oncology and Pathology, Lund University, Lund 221 85, Sweden.
  • 7 Department of Translational Medicine, Clinical Pathology, Skånes Universitetssjukhus, Malmö 205 02, Sweden.
PMID: 27725631 DOI: 10.1038/ncomms13050
Abstract

Triple-negative (TN) breast cancers (ER-PR-HER2-) 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.

Figures
Products