title: A functional in vitro model of heterotypic interactions reveals a role for interferon-positive carcinoma associated fibroblasts in breast cancer.
abstract: BACKGROUND
  Cancer-associated fibroblasts (CAFs) play an important role in breast cancer pathogenesis by paracrine regulation of breast cancer cell biology. Several in vitro and mouse models have characterized the role of cell contact and cytokine molecules mediating this relationship, although few reports have used human CAFs from breast tumors.
  
  
  METHODS
  Primary breast CAF cultures were established and gene expression profiles analysed in order to guide subsequent co-culture models. We used a combination of colorimetric proliferation assays and gene expression profiling to determine the effect of CAFs on the MCF-7 breast cancer cell in an indirect co-culture system.
  
  
  RESULTS
  Using gene expression profiling, we found that a subgroup of breast CAFs are positive for a type one interferon response, confirming previous reports of an activated type one interferon response in whole tumor datasets. Interferon positive breast cancer patients show a poor prognostic outcome in an independent microarray dataset. In addition, CAFs positive for the type one interferon response promoted the growth of the MCF-7 breast cancer cell line in an indirect co-culture model. The addition of a neutralizing antibody against the ligand mediating the type one response in fibroblasts, interferon-β, reverted this co-culture phenotype. CAFs not expressing the interferon response genes also promoted the growth of the MCF-7 breast cancer cell line but this phenotype was independent of the type one fibroblast interferon ligand.
  
  
  CONCLUSIONS
  Primary breast CAFs show inter-patient molecular heterogeneity as evidenced by interferon response gene elements activated in a subgroup of CAFs, which result in paracrine pro-proliferative effects in a breast cancer cell line co-culture model.
authors.affiliation: Lady Davis Institute for Medical Research, Sir Mortimer B. Davis Jewish General Hospital, Montreal, Canada. abdelhosein@gmail.com.|Department of Pharmacology & Therapeutics, McGill University, Montreal, Canada. abdelhosein@gmail.com.
authors.forename: Abdel Nasser
authors.initials: AN
authors.lastname: Hosein
authors.affiliation: McGill Centre for Bioinformatics, Montreal, Canada. julie.marie.livingstone@gmail.com.
authors.forename: Julie
authors.initials: J
authors.lastname: Livingstone
authors.affiliation: Lady Davis Institute for Medical Research, Sir Mortimer B. Davis Jewish General Hospital, Montreal, Canada. magbuchn@gmail.com.
authors.forename: Marguerite
authors.initials: M
authors.lastname: Buchanan
authors.affiliation: Fondazione IFOM Istituto FIRC di Oncologia Molecolare, Milan, Italy. james.reid@ifom-ieo-campus.it.
authors.forename: James F
authors.initials: JF
authors.lastname: Reid
authors.affiliation: McGill Centre for Bioinformatics, Montreal, Canada. hallett@mcb.mcgill.ca.
authors.forename: Michael
authors.initials: M
authors.lastname: Hallett
authors.affiliation: Lady Davis Institute for Medical Research, Sir Mortimer B. Davis Jewish General Hospital, Montreal, Canada. mark.basik@mcgill.ca.|Department of Oncology, McGill University, Montreal, Canada. mark.basik@mcgill.ca.|Department of Surgery, McGill University, Montreal, Canada. mark.basik@mcgill.ca.|Department of Oncology, Lady Davis Institute, 3755 Cote Ste Catherine, Montreal, QC, H3T1E2, Canada. mark.basik@mcgill.ca.
authors.forename: Mark
authors.initials: M
authors.lastname: Basik
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism*; D018920:Coculture Techniques / Q000379:methods; D015331:Cohort Studies; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D007372:Interferons / Q000378:metabolism* / Q000494:pharmacology; D061986:MCF-7 Cells
chemical_list: D007372:Interferons