S100A4 (Mts1): is there any relation to the pathogenesis of rheumatoid arthritis?

Abstract

S100A4 (Mts1) belongs to the S100 family of calcium binding proteins, which are involved in diverse biological regulatory activities. An association between S100A4 and tumor progression has been demonstrated in several studies. S100A4 binds to distinct intracellular target proteins and regulates specific functions involved in tumor progression such as cell motility, proliferation and apoptosis as well as remodelling of the extracellular matrix. Once released from the tumor or tumor-activated stromal cells, it may influence certain functions of target cells towards a more aggressive phenotype. Extracellular S100A4 has been demonstrated to contribute to angiogenesis and the increased production of matrix-degrading enzymes by both endothelial and tumor cells. Moreover, S100A4 might be responsible for TCRgammadelta T-cell mediated lysis and negative regulation of matrix mineralization. Increased expression of S100A4 mRNA has recently been found in proliferating rheumatoid arthritis synovial fibroblasts and synovial tissues from rheumatoid arthritis patients. Synovial hyperplasia in rheumatoid arthritis consists of inflammatory cells and activated synovial lining cells which contribute to the progressive destruction of the joints during the disease. Since several phenomena are similar between rheumatoid arthritis and malignant tumors it can be hypothesized that S100A4 contributes to the invasive and tumor-like behavior of rheumatoid arthritis synovium.