By activating matrix metalloproteinase-7, shear stress promotes chondrosarcoma cell motility, invasion and lung colonization
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Pei-Pei Guan1, Xin Yu1, Jian-Jun Guo1, Yue Wang1, Tao Wang1, Jia-Yi Li1,2, Konstantinos Konstantopoulos3,4,5,6, Zhan-You Wang1, Pu Wang1
1College of Life and Health Sciences, Northeastern University, Shenyang 110819, P. R. China
2Neural Plasticity and Repair Unit, Wallenberg Neuroscience Center, Department of Experimental Medical Sciences, Lund University, Lund 22184, Sweden
3Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, Maryland 21218, United States of America
4Department of Biomedical Engineering, The Johns Hopkins University, Baltimore, Maryland 21218, United States of America
5Johns Hopkins Institute for NanoBioTechnology, The Johns Hopkins University, Baltimore, Maryland 21218, United States of America
6Johns Hopkins Physical Sciences-Oncology Center, Center of Cancer Nanotechonology Excellence, The Johns Hopkins University, Baltimore, Maryland 21218, United States of America
Pu Wang, e-mail: [email protected]
Zhan-You Wang, e-mail: [email protected]
Konstantinos Konstantopoulos, e-mail: [email protected]
Keywords: fluid shear stress, cyclic AMP, interleukin-1beta, matrix metalloproteinase 7, chondrosarcoma metastasis
Received: November 11, 2014 Accepted: February 07, 2015 Published: March 14, 2015
Interstitial fluid flow and associated shear stress are relevant mechanical signals in cartilage and bone (patho)physiology. However, their effects on chondrosarcoma cell motility, invasion and metastasis have yet to be delineated. Using human SW1353, HS.819.T and CH2879 chondrosarcoma cell lines as model systems, we found that fluid shear stress induces the accumulation of cyclic AMP (cAMP) and interleukin-1β (IL-1β), which in turn markedly enhance chondrosarcoma cell motility and invasion via the induction of matrix metalloproteinase-7 (MMP-7). Specifically, shear-induced cAMP and IL-1β activate PI3-K, ERK1/2 and p38 signaling pathways, which lead to the synthesis of MMP-7 via transactivating NF-κB and c-Jun in human chondrosarcoma cells. Importantly, MMP-7 upregulation in response to shear stress exposure has the ability to promote lung colonization of chondrosarcomas in vivo. These findings offer a better understanding of the mechanisms underlying MMP-7 activation in shear-stimulated chondrosarcoma cells, and provide insights on designing new therapeutic strategies to interfere with chondrosarcoma invasion and metastasis.
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