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

BMC Cancer

Research Article

Hélène Therriault¹  Gina Bouchard¹  Benoit Paquette¹  Rachel Bujold²  Caroline Saucier³  Yves Bérubé-Lauzière⁴  Sameh Geha⁵ 

[1] Centre for Research in Radiotherapy, Department of Nuclear Medicine and Radiobiology, Université de Sherbrooke, 3001, 12e Avenue Nord, J1H 5 N4, Sherbrooke, Québec, Canada;Centre for Research in Radiotherapy, Department of Nuclear Medicine and Radiobiology, Université de Sherbrooke, 3001, 12e Avenue Nord, J1H 5 N4, Sherbrooke, Québec, Canada;Service of Radiation Oncology, Université de Sherbrooke, Sherbrooke, Canada;Department of Anatomy and Cellular Biology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Canada;Department of Electrical and Computer Engineering, Centre d’imagerie moléculaire de Sherbrooke, Sherbrooke, Québec, Canada;Department of Pathology, Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Canada;

关键词: Chloroquine;    Inflammation;    Invasion;    Metastasis;    Radiation;    Triple negative breast cancer;   

DOI  :  10.1186/s12885-016-2393-z

 received in 2015-10-15, accepted in 2016-06-01,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundSome 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.MethodsThe 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.ResultsIrradiated 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.ConclusionCQ prevented radiation-enhancement of TNBC cell invasion and reduced the number of lung metastases in a mouse model.

【 授权许可】

CC BY   
© The Author(s). 2016