Inder Sehgal1, Katie Forbes, Matthew A Webb. 1. Center for Prostate Research, North Dakota State University, 123 Sudro Hall, Fargo, ND 58105, USA. inder.sehgal@ndsu.nodak.edu
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. 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.
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.