title: Irradiation of normal mouse tissue increases the invasiveness of mammary cancer cells.
abstract: OBJECTIVE
  Treatment of breast tumours frequently involves irradiating the whole breast to reach malignant microfoci scattered throughout the breast. In this study, we determined whether irradiation of normal tissues could increase the invasiveness of breast cancer cells in a mouse model.
  
  
  METHODS
  Non-irradiated MC7-L1 mouse mammary carcinoma cells were injected subcutaneously in irradiated and non-irradiated thighs of Balb/c mice. The invasion volume, tumour volume, blood vessel permeability and interstitial volumes were monitored by magnetic resonance imaging (MRI). Slices of normal tissue invaded by cancer cells were examined by histology. Activity of matrix metalloproteinase -2 and -9 (MMP -2 and -9) in healthy and irradiated tissues was determined, and the proliferation index of the invading cancer cells was evaluated.
  
  
  RESULTS
  Three weeks after irradiation, enhancement of MC7-L1 cells invasiveness in irradiated thighs was already detected by MRI. The tumour invasion volume continued to extend 28- to 37-fold compared to the non-irradiated implantation site for the following three weeks, and it was associated with an increase of MMP-2 and -9 activities in healthy tissues. The interstitial volume associated with invading cancer cells was significantly larger in the pre-irradiated sites; while the blood vessels permeability was not altered. Cancer cells invading the healthy tissues were proliferating at a lower rate compared to non-invading cancer cells.
  
  
  CONCLUSIONS
  Implantation of non-irradiated mammary cancer cells in previously irradiated normal tissue enhances the invasive capacity of the mammary cancer cells and is associated with an increased activity of MMP-2 and -9 in the irradiated normal tissue.
authors.affiliation: Centre de Recherche en Radiothérapie, Department of Nuclear Medicine and Radiobiology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Québec, Canada.
authors.forename: Rosalie
authors.initials: R
authors.lastname: Lemay
authors.forename: Mélanie
authors.initials: M
authors.lastname: Archambault
authors.forename: Luc
authors.initials: L
authors.lastname: Tremblay
authors.forename: Rachel
authors.initials: R
authors.lastname: Bujold
authors.forename: Martin
authors.initials: M
authors.lastname: Lepage
authors.forename: Benoit
authors.initials: B
authors.lastname: Paquette
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D008279:Magnetic Resonance Imaging / Q000379:methods; D015674:Mammary Neoplasms, Animal / Q000378:metabolism* / Q000532:radiotherapy*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D011878:Radiotherapy / Q000379:methods
chemical_list: D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9