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

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.

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

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.

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.