By activating matrix metalloproteinase-7, shear stress promotes chondrosarcoma cell motility, invasion and lung colonization.
Författare
Summary, in English
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.
Avdelning/ar
Publiceringsår
2015
Språk
Engelska
Sidor
9140-9159
Publikation/Tidskrift/Serie
Oncotarget
Volym
6
Issue
11
Fulltext
- Available as PDF - 12 MB
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Länkar
Dokumenttyp
Artikel i tidskrift
Förlag
Impact Journals
Ämne
- Cancer and Oncology
Status
Published
Forskningsgrupp
- Neural Plasticity and Repair
ISBN/ISSN/Övrigt
- ISSN: 1949-2553