Irradiation of normal mouse tissue increases the invasiveness of mammary cancer cells

Abstract

Purpose: 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.

Materials and 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.

Conclusion: 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.

Keywords:

• breast cancer
• invasion
• magnetic resonance imaging
• radiotherapy

Acknowledgements

BP, RB and ML are members of the FRSQ-funded Centre de recherche clinique Étienne-LeBel, ML is the Canada Research Chair in magnetic resonance imaging, RL received a student stipend from the NSERC. The authors would like to thank Dr Ana-Maria Crous Tsanaclis form the Department of Pathology of the Centre Hospitalier Universitaire de Sherbrooke for her contribution in the histological evaluation of normal tissues invaded by cancer cells. The authors would like to thank Dr Léonid Volkov for his helpful contribution in the quantification of cancer cell invasion by histology assay. This research program was supported by the Canadian Institutes of Health Research and the Canadian Breast Cancer Research Alliance (Grant No. 184671).

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.