Interleukin-1β and cyclic AMP mediate the invasion of sheared chondrosarcoma cells via a matrix metalloproteinase-1-dependent mechanism.
Matrix metalloproteinase-1 (MMP-1) is a potential biomarker for chondrosarcoma that is overexpressed at the invading edges of articular cartilage, and its expression correlates with poor survival rates. However, the molecular mechanisms of MMP-1 regulation and its potential contribution to chondrosarcoma cell invasion have yet to be elucidated, especially in shear-activated cells. Using molecular biology tools and an in vitro fluid shear model, we report that shear stress upregulates cyclic AMP (cAMP) and interleukin-1β (IL-1β) release, which in turn promotes the invasion of chondrosarcoma cells via the induction of MMP-1 in a phosphoinositide 3-kinase (PI3-K)- and ERK1/2-dependent manner. Activated PI3-K and ERK1/2 signaling pathways phosphorylate c-Jun, which in turn transactivates MMP-1 in human chondrosarcoma cells. Collectively, fluid shear stress upregulates matrix MMP-1 expression, which is responsible for the enhanced invasion of human chondrosarcoma cells.
College of Life and Health Sciences, Northeastern University, Shenyang 110819, PR China; Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, MD, USA.
Pu
P
Wang
College of Life and Health Sciences, Northeastern University, Shenyang 110819, PR China; Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, MD, USA.
Pei-Pei
PP
Guan
College of Life and Health Sciences, Northeastern University, Shenyang 110819, PR China.
Tao
T
Wang
College of Life and Health Sciences, Northeastern University, Shenyang 110819, PR China.
Xin
X
Yu
College of Life and Health Sciences, Northeastern University, Shenyang 110819, PR China.
Jian-Jun
JJ
Guo
Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, MD, USA; Johns Hopkins Institute for NanoBio Technology, The Johns Hopkins University, Baltimore, MD, USA; Johns Hopkins Physical Sciences-Oncology Center, The Johns Hopkins University, Baltimore, MD, USA; Center of Cancer Nanotechonology Excellence, The Johns Hopkins University, Baltimore, MD 21218, USA.
Konstantinos
K
Konstantopoulos
College of Life and Health Sciences, Northeastern University, Shenyang 110819, PR China. Electronic address: wangzy@mail.neu.edu.cn.
Zhan-You
ZY
Wang
D001483:Base Sequence; D045744:Cell Line, Tumor; D002813:Chondrosarcoma / Q000201:enzymology / Q000473:pathology* / Q000503:physiopathology; D047369:Chromatin Immunoprecipitation; D003470:Culture Media; D000242:Cyclic AMP / Q000502:physiology*; D017931:DNA Primers; D006801:Humans; D053583:Interleukin-1beta / Q000502:physiology*; D020935:MAP Kinase Signaling System; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction
D003470:Culture Media; D017931:DNA Primers; D053583:Interleukin-1beta; D000242:Cyclic AMP; D020781:Matrix Metalloproteinase 1
Cyclic AMP; Fluid shear stress; Interleukin-1β; Invasion; Matrix metalloproteinase-1; c-Jun