Reduced secretion of MMPs, plasminogen activators and TIMPS from prostate cancer cells derived by repeated metastasis.
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.
Sehgal
Inder
I
Center for Prostate Research, North Dakota State University, 123 Sudro Hall, Fargo, ND 58105, USA. inder.sehgal@ndsu.nodak.edu
Forbes
Katie
K
Webb
Matthew A
MA
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
D005353:Fibronectins; D017395:Plasminogen Activator Inhibitor 1; D019714:Tissue Inhibitor of Metalloproteinases; D010960:Plasminogen Activators; D020782:Matrix Metalloproteinases