Interleukin-1β and cyclic AMP mediate the invasion of sheared chondrosarcoma cells via a matrix metalloproteinase-1-dependent mechanism

Pu Wang, Pei Pei Guan, Tao Wang, Xin Yu, Jian Jun Guo, Konstantinos Konstantopoulos, Zhan You Wang

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)923-933
Number of pages11
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Volume1843
Issue number5
DOIs
StatePublished - May 1 2014

Keywords

  • C-Jun
  • Cyclic AMP
  • Fluid shear stress
  • Interleukin-1β
  • Invasion
  • Matrix metalloproteinase-1

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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