S100A4 protein belongs to the large group of calcium binding protein family that consists of more than 25 low-weight molecules and appears to play regulatory roles in diverse biological activities. The S100A4 protein participates in the regulation of cell motility, proliferation and apoptosis, angiogenesis and remodeling of extracellular matrix. Functional role of S100A4 is associated with metastasis and the protein is suggested as a prognostic marker for various types of cancers. Increased expression of S100A4 mRNA was recently detected in proliferating synovial fibroblasts in rheumatoid arthritis (RA). Up-regulation of S100A4 protein in RA synovial tissue compared with osteoarthritic and control tissues have been also demonstrated. Moreover, the protein has been found at the sites of joint invasion. S100A4 is produced not only by synovial fibroblasts but also by several immune and vascular cells. Increased amount of bioactive S100A4 oligomer was determined not only locally at the inflammatory synovial tissue but also in plasma and synovial fluid. Consistently with the data in cancer studies, extracellular S100A4 oligomer can stimulate production of several matrix degrading enzymes – metaloproteinases and modulate biological function of the tumor suppressor protein p53 in synovial fibroblasts. Taken together, one can speculate that increased S100A4 protein might be implicated in the process of aggressive fibroblast behavior contributing to the pathogenesis of chronic autoimmune inflammatory rheumatic diseases.

        Key words: rheumatoid arthritis, S100A4, apoptosis, matrix degrading enzymes, synovial fibroblasts