Interferon-gamma induced Serine protease, Epithin./Matrpatse in macrophage through JAK/STAT Pathway

초록

Epithin/Matriptase is a type II transmembrane serine protease (TTSP) that is originally found to be expressed in the subpopulation of epithelial cells. Epithin/matriptase was reported to be overexpressed in a variety of epithelial cancers. Epithin/matriptase is involved in the degradation of ECM components and in activation of pro-HGF and pro-uPA, which elevate the invasiveness of tumor cells. Through the studies with transgenic mouse models, it is now clear that epithin/matriptase is associated with cancer development and metastasis, although the precise mechanisms, how epithin/matriptase works in those processes, are not very clear. It is also reported that epithin/matriptase activate pro-MSP (macrophage stimulating protein) which is has a function in cancer progression. In these studies, we show that macrophages activated by the treatment of interferon- showed the increased levels of epithin mRNA and protein. We also show that Epithin, in cis and in trans, interacts and cleaves angiopoietin receptor Tie2 that plays essential roles in vessel stability. These data suggest that epithin present in the activated macrophage may provide the cue for cancer cells to transmigrate endothelial cells.