In chronic inflammation extracellular matrix (ECM) proteins are frequently citrullinated. We have shown that citrullination of ECM proteins, such as collagens and fibronectin, can also affect cellular interactions, e.g. integrin-mediated cell adhesion. In an analysis of 40 synovial fluid samples derived from chronically inflamed human joints we detected citrullination of 55 arginine recidues in extracellular proteins. Many of the sites had a characterized function related to the hallmarks of destructive joint inflammation. We have also extended our studied on citrullination of matrisome proteins in cancer. In this purpose we analyzed cancer proteomics data sets in 3 public databases for citrullinated matrisome proteins. While we detected citrullination of ECM, there was significant variation between tumors. Most frequently citrullinated proteins included fibrinogen and fibronectin, which are typically citrullinated in rheumatoid inflammation. We also detected correlation between immune cell marker proteins, matrix metalloproteinases and ECM citrullination, which suggests that in cancer, citrullination of matrisome proteins is predominantly an inflammation-related phenomenon.
In addition, we have developed three-dimensional cell culture methods to study ECM citrullination in experimental conditions.