A carcinoma marker, PRSS14/epithin mediates the transendothelial migration of macrophage activated with IFNg through JAK/STAT pathway

초록

A carcinoma marker, PRSS14/Epithin/Matriptase (Type II Membrane Type Serine Protease) Mediates the Transendothelial Migration of Macrophages Activated with IFN-g through JAK/STAT1 Pathway Deokjae Lee and Moon Gyo Kim 1Department of Biological Sciences, Inha University, Incheon 402-751, Republic of Korea, 1. Abstract PRSS14/Epithin (matriptase, ST14), a type II transmembrane serine proteases, is a new epithelial cancer marker. We showed earlier that PRSS14/Epithin is critically involved in the transendothelila migration of cancer cells through proteolytically regulating the angiopoietin receptor Tie2 protein expressed on the endothelial cells and in the metastasis of breast cancer cell 4T1 in Blab/c mouse. Its expression was found to be upregulated in macrophage cell lines and bone marrow derived primary macrophage upon activation by IFN-, but not by TNF or TGF. The mechanism of induction is at the levels of transcription as well as post-transcription. Transcriptional induction by IFN- is in the downstream of JAK pathway, tested using specific inhibitors. By chromating immunoprecipitation, we found that two out of six putative STAT1 binding sites in the upstream PRSS14/Epithin promoter are involved during induction. Treatment of IFN- enhanced the serum-triggered transendothelial migration of macrophages though mouse MS1 endothelial cells. The abrogation of transendothelial migration by knock down in the macrophage is apparent. 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 provided evidence 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.