CXCL14 is a cytokine from the CXC chemokine or BRAK (breast and kidney-expressed chemokine) family. It was first identified at the turn of the 21st century in head and neck cancer, where it was found to decrease in tumours. It is reduced in or absent from most cancer cells and is a chemoattractant, as well as inhibiting angiogenesis. CXCL14 can be linked to a number of physiological diseases and their diagnoses, and also has some significances in the field of psychiatry and mental health. CXCL14 can be viewed in several different therapeutic, diagnostic and analytical contexts, including the inhibition of growth of tumours.
CXCL14 is an antimicrobial gene and the cytokine family it belongs to encodes proteins related to regulating the immune system and inflammatory processes. The gene codes a protein related to the CXC or BRAK subfamily, which consists of proteins with two cysteines separated by a single amino acid. CXCL14 protein demonstrates chemotaxis for monocytes, but it does not respond to lymphocytes, dendritic cells, neutrophils, or macrophages. It might relate to the homeostasis of monocyte-derived macrophages. CXCL14 inhibits endothelial cell chemotaxis in vitro when introduced to CXCL8, as well as bFGF and VEGF. In vivo, it responds to these by inhibiting angiogenesis. Non-lymphoid tissues such as kidney, breast a gut tissues, express BRAK.
A number of diseases are associated with CXCL14, including head and neck squamous cell carcinoma and pelvic lipomatosis. The majority of HNSCC and some cervical squamous cell carcinoma do not express CXCL14 mRNA. Localized prostate cancer, on the other hand, shows an increase in CXCL14 mRNA. The chemotactic effect can be blocked by an antiserum against CXCL14 or by pertussis toxin. Tumour myoepithelial cells and myofibroblasts with an overexpression of CXCL14 and CXCL12 have enhanced proliferation and migration of epithelial cells due to the chemokines binding to their receptors. BRAK strongly inhibits angiogenesis and stimulates immature dendritic cells in the immune system.
A 2005 study has shown that LAPC4 cells that express CXCL14 show a 43% tumour growth inhibition compared to vector only xenografts. Upregulated CXCL14 in localized prostate cancer has been shown to positively correlate with Gleason scores. This shows that CXCL14 could be used to suppress tumours as one possible therapeutic application. Further studies have continued to show CXCL14 as an emerging regulator of inflammatory processes and immune response. It could also influence other chemokine functions, such as CXCL12. More research, particularly focusing on finding the receptor for BRAK could help to find the mechanisms it uses to influence immune response.
Further research into CXCL14 could reveal a lot more about how it functions. Its therapeutic applications could become more apparent with more studies in the future, which will hopefully offer insight into how BRAK functions. It could assist with advancements in encouraging immune responses and treatment of certain cancers. As a gene that was identified relatively recently, there is still a lot to learn about CXCL14. BRAK is available as human, mouse or rat recombinant as a sterile, filtered, freeze-dried powder that is shipped at room temperature.