Editorial [Hot topic: Innate Immunity Molecules S100A8/A9 Involved in Stress Response and Cancer Biology (Guest Editors: Claus Kerkhoff and Saeid Ghavami)]

Members of the S100 protein family comprise a multigenic group of non-ubiquitous cytoplasmic Ca2+-binding proteins of the EF-hand type, differentially expressed in a wide variety of cell types. They are small acidic proteins (10-12 kDa) that are found exclusively in vertebrates, and have been implicated in the regulation of many diverse processes such as signal transduction, cell growth and motility, cell-cycle regulation, transcription, differentiation, and cell survival. A large number of different human diseases have been associated with the variety of S100 proteins and their defective functions, e.g., cancer, inflammation, cardiomyopathies, neurodegenerative diseases, and allergies. Most S100 genes are located in a gene cluster near a region on human chromosome 1q21, which is responsible for a number of chromosomal abnormalities and has been frequently rearranged in human cancer. In addition, the S100 gene cluster is close to the epidermal differentiation complex as well as to a psoriasis susceptibility region, the PSORS4 locus. These data are important indications for the involvement of S100 genes in inflammatory as well as neoplastic disorders. The rearrangements may result in a deregulated expression of S100 genes associated with neoplasia. Furthermore, there is also an extensive interest in researching the possibility of using S100 proteins/specific antibodies in clinical diagnosis. It is worth mentioning that the first link between S100 family members and a specific disease was made for S100A8 and S100A9. It was speculated for considerable time that these two proteins could represent the proteins responsible for cystic fibrosis, a speculation now superseded by the cloning of the gene encoding the membrane protein cystic fibrosis conductance regulator. Nevertheless, it has been shown that S100A8- and S100A9-expressing cells belong to the early infiltrating cells and dominate acute inflammatory lesions. Phagocytes expressing S100A8 and S100A9 are found in a variety of inflammatory conditions, including rheumatoid arthritis, allograft rejections, and inflammatory bowel and lung diseases. Inflammatory disorders such as chronic bronchitis, cystic fibrosis, and rheumatoid arthritis are associated with elevated plasma levels of S100A8/A9. There are high correlations between S100A8/A9 plasma concentrations and clinical and laboratory markers of inflammation, as well as the rapid normalization following clinical improvement suggesting that these proteins track disease activity. Therefore, S100A8 and S100A9 are widely used as marker proteins for activated or recruited phagocytes as well as a diagnostic marker for disease activity. However, over the last decade they have gained increasing interest in many files of medicine due to their deregulated epidermal expression as a response to stress and in association with neoplastic disorders. S100A8 and S100A9 are predominantly expressed in myeloid cells. Except for inflammatory conditions, the expression of S100A8 and S100A9 is restricted to a specific stage of myeloid differentiation since both proteins are expressed in circulating neutrophils and monocytes but are absent in normal tissue macrophages and lymphocytes. Under chronic inflammatory conditions, such as psoriasis and malignant disorders, they are also expressed in the epidermis.