title: Cancer-associated fibroblast-secreted CXCL16 attracts monocytes to promote stroma activation in triple-negative breast cancers.
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.
authors.affiliation: Department of Translational Medicine, Cancer Immunology, Lund University, Malmö 205 02, Sweden.
authors.forename: Roni
authors.initials: R
authors.lastname: Allaoui
authors.affiliation: Department of Translational Medicine, Cancer Immunology, Lund University, Malmö 205 02, Sweden.
authors.forename: Caroline
authors.initials: C
authors.lastname: Bergenfelz
authors.affiliation: Department of Laboratory Medicine, Translational Cancer Research, Lund University, Lund 223 63, Sweden.
authors.forename: Sofie
authors.initials: S
authors.lastname: Mohlin
authors.affiliation: Department of Translational Medicine, Cancer Immunology, Lund University, Malmö 205 02, Sweden.|Department of Anatomy and the Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California 94143-0452, USA.
authors.forename: Catharina
authors.initials: C
authors.lastname: Hagerling
authors.affiliation: Department of Anatomy and the Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California 94143-0452, USA.
authors.forename: Kiarash
authors.initials: K
authors.lastname: Salari
authors.affiliation: Department of Anatomy and the Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California 94143-0452, USA.
authors.forename: Zena
authors.initials: Z
authors.lastname: Werb
authors.affiliation: Sir Peter MacCallum Department of Oncology, Peter MacCallum Cancer Centre, The University of Melbourne, Melbourne 8006, Australia.
authors.forename: Robin L
authors.initials: RL
authors.lastname: Anderson
authors.affiliation: Department of Pathology and Laboratory Medicine, Hollings Cancer Center, Medical University of South Carolina, Charleston, South Carolina 29425, USA.
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Ethier
authors.affiliation: Department of Clinical Sciences Lund, Oncology and Pathology, Lund University, Lund 221 85, Sweden.
authors.forename: Karin
authors.initials: K
authors.lastname: Jirström
authors.affiliation: Department of Laboratory Medicine, Translational Cancer Research, Lund University, Lund 223 63, Sweden.
authors.forename: Sven
authors.initials: S
authors.lastname: Påhlman
authors.affiliation: Department of Laboratory Medicine, Translational Cancer Research, Lund University, Lund 223 63, Sweden.
authors.forename: Daniel
authors.identifier: 0000-0001-9426-9550
authors.initials: D
authors.lastname: Bexell
authors.affiliation: Department of Translational Medicine, Clinical Pathology, Skånes Universitetssjukhus, Malmö 205 02, Sweden.
authors.forename: Balázs
authors.initials: B
authors.lastname: Tahin
authors.affiliation: Department of Translational Medicine, Cancer Immunology, Lund University, Malmö 205 02, Sweden.|Department of Translational Medicine, Clinical Pathology, Skånes Universitetssjukhus, Malmö 205 02, Sweden.
authors.forename: Martin E
authors.initials: ME
authors.lastname: Johansson
authors.affiliation: Department of Laboratory Medicine, Translational Cancer Research, Lund University, Lund 223 63, Sweden.
authors.forename: Christer
authors.initials: C
authors.lastname: Larsson
authors.affiliation: Department of Translational Medicine, Cancer Immunology, Lund University, Malmö 205 02, Sweden.
authors.forename: Karin
authors.identifier: 0000-0001-8254-3137
authors.initials: K
authors.lastname: Leandersson
mesh_terms: D000818:Animals; D000072645:Cancer-Associated Fibroblasts / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D000075743:Chemokine CXCL16 / Q000378:metabolism*; D002630:Chemotactic Factors / Q000494:pharmacology*; D018920:Coculture Techniques; D003094:Collagen / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007165:Immunosuppression Therapy; D008819:Mice, Nude; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D022423:Myeloid Cells / Q000378:metabolism / Q000473:pathology; D012995:Solubility; D017154:Stromal Cells / Q000473:pathology; D064726:Triple Negative Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D059016:Tumor Microenvironment / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: C423727:CXCL16 protein, human; D000075743:Chemokine CXCL16; D002630:Chemotactic Factors; D003094:Collagen