Reduced secretion of MMPs, plasminogen activators and TIMPS from prostate cancer cells derived by repeated metastasis

Anticancer Res. Jan-Feb 2003;23(1A):39-42.


Background: Although prostate cancer metastasis is usually assumed to originate from the prostate gland itself, metastatic-derived human cell lines readily metastasize in vivo suggesting that metastases may metastasize. To determine if this additional selection produces changes in the expression of metastasis-associated characteristics, we compared PC-3 cells with two PC-3 derivatives from progressive cycles of re-metastasis.

Materials and methods: MMPs, TIMPs, plasminogen activators and PAI-1 as well as growth rate and adhesion to fibronectin were assessed.

Results: Levels of MMP-1, uPA and tPA decreased in PC-3M and/or PC-3MM2 compared with PC-3 cells. TIMPs and PAI-1 levels were also reduced in the metastasis-derived cells. However, both re-metastasized lines possessed much higher growth rates and fibronectin adhesiveness.

Conclusion: Re-metastasizing cells may have reduced protease secretion and therefore rely more on the availability of paracrine proteases; however characteristics such as reduced production of protease inhibitors, faster growth rate and greater adhesiveness may promote re-metastasis.

Publication types

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

MeSH terms

  • Animals
  • Cell Adhesion / physiology
  • Cell Division / physiology
  • Fibronectins / metabolism
  • Humans
  • Liver Neoplasms, Experimental / enzymology
  • Liver Neoplasms, Experimental / metabolism
  • Male
  • Matrix Metalloproteinases / metabolism*
  • Mice
  • Mice, Nude
  • Neoplasm Transplantation
  • Plasminogen Activator Inhibitor 1 / metabolism
  • Plasminogen Activators / metabolism*
  • Prostatic Neoplasms / enzymology
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / pathology
  • Tissue Inhibitor of Metalloproteinases / metabolism*
  • Transplantation, Heterologous
  • Tumor Cells, Cultured


  • Fibronectins
  • Plasminogen Activator Inhibitor 1
  • Tissue Inhibitor of Metalloproteinases
  • Plasminogen Activators
  • Matrix Metalloproteinases