CXCL14

CXCL14 (also known as breast and kidney-expressed chemokine (BRAK)), as a non-ELR CXC chemokine. CXCL14 displays chemotactic activity for monocytes but not for B and T cells. CXCL14 is involved in cancer, immune responses, and epithelial cell proliferation and migration. CXCL14 is a potent inhibitor of angiogenesis, and also shows antimicrobial activity. The chemokine CXCL14 is a highly conserved, homeostatic chemokine which is constitutively expressed in several normal tissues including adipose, brain, breast, cervix, lung, kidney, and skin. CXCL14 is involved in infectious and inflammatory diseases, angiogenesis, and cancer^[1][2].
Among chemokines, CXCL14 is highly conserved in mammals with only two amino acids difference between mice and humans. CXCL14 has four conserved cysteine residues that form disulfide bonds7. Also, in common, the first 22 amino acids of the N-terminus are strongly hydrophobic and act as a signal peptide, which is cleaved prior to secretion. Like other chemokines, CXCL14 is a chemoattractant, especially for monocytes, and induces maturation and migration of dendritic cells (DCs). However, the CXCL14-related migration of monocyte in the absence of prostaglandin E2 (PGE2) is weak, showing that PGE2 is required for CXCL14-related chemotaxis. Responsiveness of monocytes to CXCL14 and PGE2 is specific, and B and T cells do not have any chemotactic response. In addition to monocytes, CXCL14 specifically increases chemotaxis of CD56+ natural killer (NK) cells. Responsible for immune cell recruitment and maturation, as well as impacting epithelial cell motility, CXCL14 contributes to the establishment of immune surveillance within normal epithelial layers. Overall, CXCL14 is responsible for the infiltration of immune cells, maturation of dendritic cells, upregulation of major histocompatibility complex (MHC)-I expression, and cell mobilization. Although fibroblast-derived CXCL14 has a tumor-supportive role, epithelial-derived CXCL14 mainly inhibits tumor progression^[1][2].