Membrane type 1-matrix metalloproteinase promotes human prostate cancer invasion and metastasis

Thromb Haemost. 2005 Apr;93(4):770-8. doi: 10.1160/TH04-08-0555.


Development of metastases requires cancer cells to breach underlying basement membrane, migrate through interstitial stroma and gain access to blood or lymphatic vessels. Membrane type 1-matrix metalloproteinase (MT1-MMP) has been linked with these processes. Expression of MT1-MMP in human prostate cancer correlates with the stage of this disseminated disease. The mechanism underlying this observation, however, still remains to be understood. To study the role of MT1-MMP in prostate cancer dissemination, endogenous and recombinant MT1-MMP expressed in human prostate cancer cell lines (DU-145 and LNCaP) were examined. Using FITC-labeled Matrigel, a soluble basement membrane extract coated coverslips, LNCaP cells stably expressing a chimera of MT1-MMP and Green Fluorescent Protein (MT1-GFP) degraded Matrigel and readily migrated over degraded substrates. The degradation of Matrigel by LNCaP cells expressing MT1-GFP was sensitive to MMP inhibitors, CT-1746 and TIMP-2, but not TIMP-1. Cell migration was dramatically enhanced by expression of MT1-MMP. By employing surgical orthotopic implantation of LNCaP cells stably expressing MT1-GFP into the prostate gland of immunodeficient mice, we demonstrated that MT1-MMP promotes lymph node and lung metastasis of prostate cancer cells. Together, these results emphasize the pivotal role of MT1-MMP in prostate cancer dissemination and confirm that MT1-MMP is a suitable target to prevent cancer metastasis.

Publication types

  • Research Support, N.I.H., Extramural
  • 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
  • Basement Membrane / metabolism
  • Cell Line, Tumor
  • Cell Movement
  • Humans
  • Lung Neoplasms / secondary
  • Lymph Nodes / pathology
  • Male
  • Matrix Metalloproteinase 14
  • Matrix Metalloproteinases, Membrane-Associated
  • Metalloendopeptidases / genetics
  • Metalloendopeptidases / physiology*
  • Mice
  • Mice, Nude
  • Neoplasm Invasiveness / pathology*
  • Neoplasm Metastasis / pathology*
  • Neoplasm Transplantation
  • Prostatic Neoplasms / enzymology
  • Prostatic Neoplasms / etiology
  • Prostatic Neoplasms / pathology*
  • Transfection


  • Mmp14 protein, mouse
  • Matrix Metalloproteinases, Membrane-Associated
  • Metalloendopeptidases
  • Matrix Metalloproteinase 14