Abstract A54: Downregulation of hepatocyte growth factor activator inhibitor-2 is involved in the progression of prostate cancer cells

Abstract

Abstract Dysregulation of pericellular proteolysis has been strongly involved in tumorigenesis. In this study, we delineated the role of hepatocyte growth factor activator inhibitor-2 (HAI-2) in prostate cancer cell invasion and tumorigenicity within a human prostate cancer progression model (103E, N1, and N2 cells). This model was newly established by a serial of intraprostatic propagation of a human prostate cancer 103E cell line and isolation of the metastatic cells from nearby lymph nodes. The invasion capability of these cells was gradually increased after the serial isolations (103E<N1 <N2). In this series of cells, the expression of HAI-2 was significantly decreased during the progression. Following the course of orthotopic tumor growth in mice, the expression level and activity of a HAI-2 target, matriptase, increased while the HAI-2 protein level decreased. Restoration of HAI-2 expression in N2 cells down-regulated the matriptase activity and cell proliferation, thus decreased the tumorigenicity. These results show that during the progression of human prostate cancer, matriptase was primarily controlled by HAI-2 expression. The imbalance in HAI-2 and matriptase expression led to matriptase activation, therefore increased cell invasion and tumorigenicity. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr A54.