Hepsin promotes prostate cancer progression and metastasis

Cancer Cell. 2004 Aug;6(2):185-95. doi: 10.1016/j.ccr.2004.07.008.


The majority of cancer-related deaths are associated with metastasis; however, little is known about the mechanisms of this process. Hepsin is a cell surface serine protease that is markedly upregulated in human prostate cancer; however, the functional significance of this upregulation is unknown. We report here that hepsin overexpression in prostate epithelium in vivo causes disorganization of the basement membrane. Overexpression of hepsin in a mouse model of nonmetastasizing prostate cancer has no impact on cell proliferation, but causes disorganization of the basement membrane and promotes primary prostate cancer progression and metastasis to liver, lung, and bone. We provide in vivo evidence that upregulation of a cell surface serine protease in a primary tumor promotes cancer progression and metastasis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Apoptosis
  • Basement Membrane / metabolism
  • Basement Membrane / pathology
  • Basement Membrane / ultrastructure
  • Cell Differentiation
  • Cell Division
  • Disease Models, Animal
  • Disease Progression
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Transgenic
  • Neoplasm Metastasis*
  • Prostate / anatomy & histology
  • Prostate / metabolism
  • Prostate / pathology
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / pathology*
  • Serine Endopeptidases / genetics
  • Serine Endopeptidases / metabolism*


  • Membrane Proteins
  • Serine Endopeptidases
  • hepsin