common usage of PRSS14/epithin in transendothelial migration between metastatic cancer anf the activated macrophage

초록

PRSS14/Epithin (also known as matriptase, and ST14), a member of type II transmembrane serine proteases, is upregulated in epithelial cancers and activated macrophages. Surface and cytoplasmic expression in macrophage cell lines and bone marrow derived primary macrophage was induced upon activation by IFN-, but not by TNF or TGF while in epithelial cancer cells, induced by TGF. Induction mechanism is transcriptional as well as post-transcriptional. Transcriptional induction by IFN- is in the downstream of JAK pathway and uses 2 STAT1 binding sites of the PRSS14/Epithin promoter. Treatment of IFN- enhanced the serum-triggered transendothelial migration of macrophages, but that of knock-down macrophages. The abrogation of transendothelial migration by knock down is also apparent in the epithelial cancer cells. However, knocking down PRSS14/Epithin message in macrophage cells did not interfere other functions such as the expression of surface markers such as ICAM1, CD80, and CD40. These data strongly suggest that PRSS14/Epithin plays an important role in the transendothelial migration of activated macrophage in the inflammatory microenvironment and the mode of action is similar to the events in cancer metastasis using the angiopoietin receptor Tie2.