Oncotarget

Research Papers:

By activating matrix metalloproteinase-7, shear stress promotes chondrosarcoma cell motility, invasion and lung colonization

Pei-Pei Guan _, Xin Yu, Jian-Jun Guo, Yue Wang, Tao Wang, Jia-Yi Li, Konstantinos Konstantopoulos, Zhan-You Wang and Pu Wang

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Oncotarget. 2015; 6:9140-9159. https://doi.org/10.18632/oncotarget.3274

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Abstract

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

Correspondence to:

Pu Wang, e-mail: wangpu@mail.neu.edu.cn

Zhan-You Wang, e-mail: wangzy@mail.neu.edu.cn

Konstantinos Konstantopoulos, e-mail: konstant@jhu.edu

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

ABSTRACT

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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