title: Induction of interleukin-1β by mouse mammary tumor irradiation promotes triple negative breast cancer cells invasion and metastasis development.
abstract: Radiotherapy increases the level of inflammatory cytokines, some of which are known to promote metastasis. In a mouse model of triple negative breast cancer (TNBC), we determined whether irradiation of the mammary tumor increases the level of key cytokines and favors the development of lung metastases.
  
  
  
  D2A1 TNBC cells were implanted in the mammary glands of a Balb/c mouse and then 7 days old tumors were irradiated (4 × 6 Gy). The cytokines IL-1β, IL-4, IL-6, IL-10, IL-17 and MIP-2 were quantified in plasma before, midway and after irradiation. The effect of tumor irradiation on the invasion of cancer cells, the number of circulating tumor cells (CTC) and lung metastases were also measured.
  
  
  
  TNBC tumor irradiation significantly increased the plasma level of IL-1β, which was associated with a greater number of CTC (3.5-fold) and lung metastases (2.3-fold), compared to sham-irradiated animals. Enhancement of D2A1 cell invasion in mammary gland was associated with an increase of the matrix metalloproteinases-2 and -9 activity (MMP-2, -9). The ability of IL-1β to stimulate the invasiveness of irradiated D2A1 cells was confirmed by in vitro invasion chamber assays.
  
  
  
  Irradiation targeting a D2A1 tumor and its microenvironment increased the level of the inflammatory cytokine IL-1β and was associated with the promotion of cancer cell invasion and lung metastasis development.
authors.affiliation: a Centre for Research in Radiotherapy, Department of Nuclear Medicine and Radiobiology, Faculty of Medicine and Health Sciences , Université de Sherbrooke , Sherbrooke , Québec , Canada.
authors.forename: Gina
authors.initials: G
authors.lastname: Bouchard
authors.affiliation: a Centre for Research in Radiotherapy, Department of Nuclear Medicine and Radiobiology, Faculty of Medicine and Health Sciences , Université de Sherbrooke , Sherbrooke , Québec , Canada.
authors.forename: Hélène
authors.initials: H
authors.lastname: Therriault
authors.affiliation: b Service of Radiation Oncology , Centre Hospitalier Universitaire de Sherbrooke, Université de Sherbrooke , Sherbrooke , Québec , Canada.
authors.forename: Rachel
authors.initials: R
authors.lastname: Bujold
authors.affiliation: c Department of Anatomy and Cellular Biology, Faculty of Medicine and Health Sciences , Université de Sherbrooke , Sherbrooke , Québec , Canada.
authors.forename: Caroline
authors.initials: C
authors.lastname: Saucier
authors.affiliation: a Centre for Research in Radiotherapy, Department of Nuclear Medicine and Radiobiology, Faculty of Medicine and Health Sciences , Université de Sherbrooke , Sherbrooke , Québec , Canada.
authors.forename: Benoit
authors.initials: B
authors.lastname: Paquette
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D016207:Cytokines / Q000276:immunology*; D005260:Female; D018836:Inflammation Mediators / Q000276:immunology; D053583:Interleukin-1beta / Q000096:biosynthesis*; D008175:Lung Neoplasms / Q000276:immunology* / Q000556:secondary*; D015674:Mammary Neoplasms, Animal / Q000276:immunology / Q000532:radiotherapy; D051379:Mice; D008807:Mice, Inbred BALB C; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D011879:Radiotherapy Dosage; D064726:Triple Negative Breast Neoplasms / Q000276:immunology* / Q000532:radiotherapy*
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D053583:Interleukin-1beta
keywords: Triple negative breast cancer; circulating tumor cells; cytokine; interleukin-1b; metastasis; radiation