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, Pu Wang

Research output: Contribution to journalArticle

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 shearstimulated chondrosarcoma cells, and provide insights on designing new therapeutic strategies to interfere with chondrosarcoma invasion and metastasis.

Original languageEnglish (US)
Pages (from-to)9140-9159
Number of pages20
JournalOncotarget
Volume6
Issue number11
DOIs
StatePublished - Jan 1 2015

Keywords

  • Chondrosarcoma metastasis
  • Cyclic AMP
  • Fluid shear stress
  • Interleukin-1beta
  • Matrix metalloproteinase 7

ASJC Scopus subject areas

  • Oncology

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