The metastasis associated protein S100A4: a potential novel link to inflammation and consequent aggressive behaviour of rheumatoid arthritis synovial fibroblasts

Abstract

The metastasis associated protein S100A4: a potential novel link to inflammation and consequent aggressive behaviour of rheumatoid arthritis synovial fibroblasts The metastasis associated protein S100A4: a potential novel link to inflammation and consequent aggressive behaviour of rheumatoid arthritis synovial fibroblasts AbstractThe metastasis-associated protein S100A4 belongs to the large family of S100 calcium-binding proteins that appear 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 remodelling of the extracellular matrix. Increased expression of S100A4 mRNA has been detected in proliferating synovial fibroblasts in rheumatoid arthritis. Furthermore, strong upregulation of the S100A4 protein in rheumatoid arthritis synovial tissue compared with osteoarthritis and control tissues has been demonstrated recently, especially at sites of joint invasion. Several immune and vascular cells were also identified to be producing S100A4 within the synovium. The local upregulation of S100A4 was accompanied by high plasma and synovial fluid concentrations of the S100A4 protein existing in the bioactive oligomeric form in patients with rheumatoid arthritis. Consistent with data from cancer studies, the extracellular S100A4 oligomer appears to be involved in regulation of several matrix-degrading enzymes and modulation of the transcriptional activation function of the tumour 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 linked to the process of aggressive fibroblast behaviour contributing to the pathogenesis of chronic autoinflammatory diseases such as rheumatoid arthritis. The metastasis associated protein S100A4: a potential novel link to inflammation and consequent aggressive behavior of rheumatoid arthritis synovial fibroblasts AbstractThe 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 ...

Sustained hypoxia leads to the emergence of cells with enhanced growth, migratory, and promitogenic potentials within the distal pulmonary artery wall

“…PDGFs are well known to be secreted by monocytes and progenitor cells and to stimulate proliferation of SMC and fibroblasts (3,46). SDF-1/CXCL12 is secreted by several cell types in response to hypoxia and has been reported to stimulate SMC proliferation (7,45). Consistent with this observation, we found that hypoxia further induces the potency of promitogenic activity of dR cells.…”

“…In human PH patients, the presence of cells, expressing hematopoietic and inflammatory markers, has been documented both within and around the pulmonary vessel wall (22,23,42,74). In PAs of infants and children with PH, expression of S100A4 (also known as mts1), a calcium-binding protein associated with invasion, metastasis of cancer cells, and with augmented cell motility (5,45,54,71), has been documented, and the numbers of S100A4-expressing cells markedly increased with the severity of pulmonary vascular lesions (21,22). Recent studies in adults with idiopathic pulmonary arterial hypertension and familial pulmonary arterial hypertension have reported the presence of cells expressing hematopoietic and progenitor cell markers within the vessel wall, and cells exhibiting mesenchymal progenitor characteristics have been reported in remodeled PAs of patients with COPD (2,38,39,48,49,75).…”

Diagnostic and Prognostic Value of Metastasis Inducer S100A4 Transcripts in Plasma of Colon, Rectal, and Gastric Cancer Patients

“…[35][36][37] Therefore, patients with active inflammation processes, with coronary heart disease, or who had recently a heart attack were excluded. Patients who had a primary tumor of another entity in history or who developed a second primary tumor during follow-up were also excluded from this analysis.…”

Actin-bundling proteins in cancer progression at a glance

“…Aberrant association of filamin-A with the prion protein PrPA correlates with worse prognosis in pancreatic cancer. A secreted variant of filamin-A in the blood correlates with highgrade astrocytomas and metastatic breast cancer (Ai et al, 2011;Alper et al, 2009;Anilkumar et al, 2003;Bedolla et al, 2009;Burton et al, 2010;Castoria et al, 2011;Kwon et al, 2008;Li et al, 2010b;Li et al, 2010c;Li et al, 2009;Loy et al, 2003;Smith et al, 2007;Sy et al, 2010;Uramoto et al, 2010;Zhou et al, 2011) Formins (Minamiya et al, 2005;Oslejskova et al, 2008) T-plastin (T-fimbrin) Microvilli of epithelial and mesenchymal cells Crosslinks F-actin into straight bundles T-plastin expression is enhanced in cisplatin-resistant human cancer cell lines (Hisano et al, 1996) L-plastin Crosslinks actin into orthogonal networks by forming tetramers. Forms a scaffold for signalling complexes and keeps SMAD3 or SMAD4 inhibited.…”