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BMC Cancer
Published in: BMC Cancer 1/2016

Open Access 01-12-2016 | Research article

Stimulation of triple negative breast cancer cell migration and metastases formation is prevented by chloroquine in a pre-irradiated mouse model

Authors: Gina Bouchard, Hélène Therriault, Sameh Geha, Yves Bérubé-Lauzière, Rachel Bujold, Caroline Saucier, Benoit Paquette

Published in: BMC Cancer | Issue 1/2016

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Abstract

Background

Some triple negative breast cancer (TNBC) patients are at higher risk of recurrence in the first three years after treatment. This rapid relapse has been suggested to be associated with inflammatory mediators induced by radiation in healthy tissues that stimulate cancer cell migration and metastasis formation. In this study, the ability of chloroquine (CQ) to inhibit radiation-stimulated development of metastasis was assessed.

Methods

The capacity of CQ to prevent radiation-enhancement of cancer cell invasion was assessed in vitro with the TNBC cell lines D2A1, 4T1 and MDA-MB-231 and the non-TNBC cell lines MC7-L1, and MCF-7. In Balb/c mice, a single mammary gland was irradiated with four daily doses of 6 Gy. After the last irradiation, irradiated and control mammary glands were implanted with D2A1 cells. Mice were treated with CQ (vehicle, 40 or 60 mg/kg) 3 h before each irradiation and then every 72 h for 3 weeks. Migration of D2A1 cells in the mammary gland, the number of circulating tumor cells and lung metastasis were quantified, and also the expression of some inflammatory mediators.

Results

Irradiated fibroblasts have increased the invasiveness of the TNBC cell lines only, a stimulation that was prevented by CQ. On the other hand, invasiveness of the non-TNBC cell lines, which was not enhanced by irradiated fibroblasts, was also not significantly modified by CQ. In Balb/c mice, treatment with CQ prevented the stimulation of D2A1 TNBC cell migration in the pre-irradiated mammary gland, and reduced the number of circulating tumor cells and lung metastases. This protective effect of CQ was associated with a reduced expression of the inflammatory mediators interleukin-1β, interleukin-6, and cyclooxygenase-2, while the levels of matrix metalloproteinases-2 and −9 were not modified. CQ also promoted a blocking of autophagy.

Conclusion

CQ prevented radiation-enhancement of TNBC cell invasion and reduced the number of lung metastases in a mouse model.
Appendix
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Metadata
Title
Stimulation of triple negative breast cancer cell migration and metastases formation is prevented by chloroquine in a pre-irradiated mouse model
Authors
Gina Bouchard
Hélène Therriault
Sameh Geha
Yves Bérubé-Lauzière
Rachel Bujold
Caroline Saucier
Benoit Paquette
Publication date
01-12-2016
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2016
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-016-2393-z

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