Acute inflammation induced by the biopsy of mouse mammary tumors promotes the development of metastasis
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Development of metastasis in peripheral tissues is a major problem in the fight to cure breast cancer. Although it is becoming evident that chronic inflammation can contribute to tumor progression and metastasis, the effect of acute inflammation in primary tumor is less known. Using mouse models for breast cancer here we show that biopsy of mammary tumors increases the frequency of lung metastases. This effect is associated with the recruitment of inflammatory cells to the lung and elevated levels of certain cytokines such as IL-6 in the lung airways. Antiinflammatory treatment prior to and after the biopsy reduces the development of metastases triggered by the biopsy. In addition, while lack of IL-6 does not affect primary tumor development, it protects from increasing number of metastases upon biopsy. Thus, our studies show that in addition to chronic inflammation, acute immune response caused by invasive procedures in the primary tumor may cause an increased risk on peripheral metastases, but the risk could be decreased by anti-inflammatory treatments.
KeywordsMetastases Biopsy Surgery Inflammation Neutrophils Breast cancer LL-6 Lung Acute inflammation Chronic inflammation
This work was funded by Cabot-Wellington Foundation (M. R.), Lake Champlain Cancer Research Organization (M. R.), and P30 RR031158 (M. R.). We would like to thank the Microscopy Imaging Facility (University of Vermont, Burlington, VT) for the advise on immunohistochemistry analysis, Dr. Charles Irvin (University of Vermont) for the use of microscope for images and helpful discussion, Dr. Daniel Weis (University of Vermont) for the use of the Ki67 antibody, and Dr. Marta Cañamero (CNIO, Madrid, Spain) for helping with the pathology.
Conflict of interest
The authors declare that they have no conflict of interest.
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