期刊
ONCOTARGET
卷 6, 期 11, 页码 9140-9159出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.3274
关键词
fluid shear stress; cyclic AMP; interleukin-1beta; matrix metalloproteinase 7; chondrosarcoma metastasis
资金
- Natural Science Foundation of China [31300777, 31371091, 81200972]
- Fundamental Research Funds of China [N120520001, N120320001, N130120002]
- Liaoning Provincial Talent Support Program [LJQ2013029]
- National Institutes of Health [R01CA186286]
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-1 beta (IL-1 beta), 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-1 beta activate PI3-K, ERK1/2 and p38 signaling pathways, which lead to the synthesis of MMP-7 via transactivating NF-kappa B 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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