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The metastasis associated protein S100A4: a potential novel link to inflammation and consequent aggressive behavior of rheumatoid arthritis synovial fibroblasts
  1. L Oslejskova
  1. Institute of Rheumatology, Czech Republic
    1. M Grigorian (mg{at}cancer.dk)
    1. Institute of Cancer Biology, Denmark
      1. S Gay (steffen.gay{at}usz.ch)
      1. WHO Collaborating Center for Molecular Biology, Switzerland
        1. M Neidhart (michel.neidhart{at}usz.ch)
        1. WHO Collaborating Center for Molecular Biology, Switzerland
          1. L Senolt (seno{at}revma.cz)
          1. Institute of Rheumatology, Czech Republic

            Abstract

            The metastasis-associated protein S100A4 belongs to the large family of calcium-binding proteins that appears to play regulatory roles in diverse biological activities. Moreover, a prognostic role of S100A4 has been suggested for patients with several types of cancer. Cancer promoting properties for S100A4 have been demonstrated, particularly through its regulation of cell motility, proliferation and apoptosis, as well as by stimulation of angiogenesis and remodeling of the extracellular matrix. Increased expression of S100A4 mRNA was detected in proliferating synovial fibroblasts in rheumatoid arthritis. Furthermore, strong up-regulation of S100A4 protein in rheumatoid arthritis synovial tissue compared with osteoarthritis and control tissues has been demonstrated recently, especially at the sites of joint invasion. Several immune and vascular cells were also identified to produce S100A4 within the synovium. The local up-regulation of S100A4 was accompanied by high plasma and synovial fluid concentrations of the S100A4 protein existing in the bioactive oligomeric form in rheumatoid arthritis patients. Consistent with the data in cancer studies, the extracellular S100A4 oligomer is involved in regulation of several matrix degrading enzymes and modulates the transcriptional activation function of the tumor suppressor protein p53 in rheumatoid arthritis synovial fibroblasts. Taken together, one can speculate that increased S100A4 protein in circulation and locally at sites of inflammation, particularly at sites of joint destruction, might be implicated in the process of aggressive fibroblast behavior contributing to the pathogenesis of chronic autoinflammatory diseases such as rheumatoid arthritis.

            • S100A4
            • apoptosis
            • matrix degrading enzymes
            • rheumatoid arthritis
            • synovial fibroblasts

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