Morphine and breast tumor metastasis: the role of matrix-degrading enzymes

Afsharimani, Banafsheh, Baran, JoAnne, Watanabe, Satoshi, Lindner, Daniel, Cabot, Peter J. and Parat, Marie-Odile (2013) Morphine and breast tumor metastasis: the role of matrix-degrading enzymes. Clinical and Experimental Metastasis, Online First 1-10. doi:10.1007/s10585-013-9616-3

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Author Afsharimani, Banafsheh
Baran, JoAnne
Watanabe, Satoshi
Lindner, Daniel
Cabot, Peter J.
Parat, Marie-Odile
Title Morphine and breast tumor metastasis: the role of matrix-degrading enzymes
Journal name Clinical and Experimental Metastasis   Check publisher's open access policy
ISSN 0262-0898
Publication date 2013-09-26
Sub-type Article (original research)
DOI 10.1007/s10585-013-9616-3
Volume Online First
Start page 1
End page 10
Total pages 10
Place of publication Dordrecht, Netherlands
Publisher Springer Netherlands
Collection year 2014
Language eng
Formatted abstract
Opioids including morphine are commonly used in pain management during and after cancer surgery but have been linked to a variety of pro- and anti-tumor effects. In the present study the effect of morphine administration on the localization and growth of breast tumor cells in lungs and the level of extracellular matrix (ECM) proteases were investigated. In a mouse syngeneic model of intravenously inoculated breast cancer cells, morphine administration led to a reduction in the localization and growth of tumors in the lungs and a reduction in circulating matrix metalloproteinase-9 (MMP-9) and urokinase-like plasminogen activator (uPA). To model the involvement of non-malignant cells of the tumor microenvironment in the changes we observed in the level of proteases, we co-cultured breast cancer cells with macrophages, endothelial cells and fibroblasts. We found a significant elevation of matrix proteases as well as matrix protease inhibitors in co-cultures of breast cancer cells with macrophages or endothelial cells. Interestingly, morphine treatment of these co-cultures reduced the level of MMP-9 and increased its endogenous inhibitor, TIMP-1, thereby altering the proteolytic profile. Morphine affected the level of enzymes in co-cultures but not in cells grown individually. This suggests that anti-tumor effects of morphine observed in our in vivo model could be mediated at least in part through modulation of paracrine communication between cancer cells and non-malignant cells in the tumor microenvironment.
Keyword Breast cancer
Endothelial cells
Matrix metalloproteinase-9
Urokinase plasminogen activator
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Published online: 26 September 2013

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
School of Pharmacy Publications
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Citation counts: TR Web of Science Citation Count  Cited 7 times in Thomson Reuters Web of Science Article | Citations
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Created: Fri, 04 Oct 2013, 11:14:57 EST by Myrtle Sahabandu on behalf of School of Pharmacy