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

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 pro...

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Autores principales: Tang, Xi, Mahajan, Sumit S., Nguyen, Liem T., Béliveau, François, Leduc, Richard, Simon, Julian A., Vasioukhin, Valeri
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4012739/
https://www.ncbi.nlm.nih.gov/pubmed/24657880
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author Tang, Xi
Mahajan, Sumit S.
Nguyen, Liem T.
Béliveau, François
Leduc, Richard
Simon, Julian A.
Vasioukhin, Valeri
author_facet Tang, Xi
Mahajan, Sumit S.
Nguyen, Liem T.
Béliveau, François
Leduc, Richard
Simon, Julian A.
Vasioukhin, Valeri
author_sort Tang, Xi
collection PubMed
description 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.
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spelling pubmed-40127392014-05-09 Targeted inhibition of cell-surface serine protease Hepsin blocks prostate cancer bone metastasis Tang, Xi Mahajan, Sumit S. Nguyen, Liem T. Béliveau, François Leduc, Richard Simon, Julian A. Vasioukhin, Valeri Oncotarget Research Paper 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. Impact Journals LLC 2014-03-16 /pmc/articles/PMC4012739/ /pubmed/24657880 Text en Copyright: © 2014 Tang et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Tang, Xi
Mahajan, Sumit S.
Nguyen, Liem T.
Béliveau, François
Leduc, Richard
Simon, Julian A.
Vasioukhin, Valeri
Targeted inhibition of cell-surface serine protease Hepsin blocks prostate cancer bone metastasis
title Targeted inhibition of cell-surface serine protease Hepsin blocks prostate cancer bone metastasis
title_full Targeted inhibition of cell-surface serine protease Hepsin blocks prostate cancer bone metastasis
title_fullStr Targeted inhibition of cell-surface serine protease Hepsin blocks prostate cancer bone metastasis
title_full_unstemmed Targeted inhibition of cell-surface serine protease Hepsin blocks prostate cancer bone metastasis
title_short Targeted inhibition of cell-surface serine protease Hepsin blocks prostate cancer bone metastasis
title_sort targeted inhibition of cell-surface serine protease hepsin blocks prostate cancer bone metastasis
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4012739/
https://www.ncbi.nlm.nih.gov/pubmed/24657880
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