Abstract 1413: Hepatocyte growth factor activator inhibitor-2 inhibits prostate cancer cell migration and invasion

Dysregulation of proteolysis on cell surface has been strongly implicated in cancer cell migration and invasion. In this study, we delineated the role of hepatocyte growth factor activator inhibitor-2 (HAI-2) in prostate cancer cell migration and invasion within a human prostate cancer progression model, established by a serial of intraprostatic injections of prostate cancer cells and isolation of the invasive cells from nearby lymph nodes. The invasion capability of these cells was increased after the serial isolations. Interestingly, the expression of HAI-2 but not HAI-1 was dramatically decreased following the progression and concurrent with an increase of activated matriptase. Overexpression of HAI-2 reduced prostate cancer cell migration and invasion, at least in part due to its inhibitory role in matriptase. Following the orthotopic tumor growth in mice, the level of matriptase was increased while HAI-2 protein level was decreased. These results indicated that during the progression of human prostate cancer, HAI-2 expression was reduced, leading to constitutive matriptase activation, increased cell migration and invasion. Thus, HAI-2 exerted an inhibitory role in prostate cancer progression partly through inhibiting matripase activity. Imbalance between HAI-2 and matriptase may result in prostate tumor progression. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1413. doi:10.1158/1538-7445.AM2011-1413