Targeted inhibition of cell-surface serine protease Hepsin blocks prostate cancer bone metastasis.

Publication Type:

Journal Article

Source:

Oncotarget, Volume 5, Issue 5, p.1352-62 (2014)

Keywords:

2014, April 2014, Center-Authored Paper, Clinical Research Division, Comp Med Small Animal, Comparative Medicine Core Facility, Flow Cytometry Core Facility, Human Biology Division, Proteomics Core Facility, Scientific Imaging Core Facility

Abstract:

The development of effective therapies inhibiting prostate cancer progression and metastasis may substantially impact prostate cancer mortality and potentially reduce the rates of invasive treatments by enhancing the safety of active surveillance strategies. Hepsin (HPN) is a cell surface serine protease amplified in a subset of human sarcomas (7.2%), as well as in ovarian (10%), lung adeno (5.4%), lung squamous cell (4.5%), adenoid cystic (5%), breast (2.6%), uterine (1.7%) and colon (1.4%) carcinomas. While HPN is not amplified in prostate cancer, it is one of the most prominently overexpressed genes in the majority of human prostate tumors and genetic experiments in mice indicate that Hepsin promotes prostate cancer metastasis, particularly metastasis to the bone marrow. We report here the development, analysis and animal trial of the small-molecule Hepsin inhibitor HepIn-13. Long-term exposure to HepIn-13 inhibited bone, liver and lung metastasis in a murine model of metastatic prostate cancer. These findings indicate that inhibition of Hepsin with small-molecule compounds could provide an effective tool for attenuation of prostate cancer progression and metastasis.