title: Reduced secretion of MMPs, plasminogen activators and TIMPS from prostate cancer cells derived by repeated metastasis.
abstract: 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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Center for Prostate Research, North Dakota State University, 123 Sudro Hall, Fargo, ND 58105, USA. inder.sehgal@ndsu.nodak.edu
authors.forename: Inder
authors.initials: I
authors.lastname: Sehgal
authors.forename: Katie
authors.initials: K
authors.lastname: Forbes
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Webb
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D008114:Liver Neoplasms, Experimental / Q000201:enzymology / Q000378:metabolism; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D010960:Plasminogen Activators / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism*; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
chemical_list: D005353:Fibronectins; D017395:Plasminogen Activator Inhibitor 1; D019714:Tissue Inhibitor of Metalloproteinases; D010960:Plasminogen Activators; D020782:Matrix Metalloproteinases