Amplification of MMP-2 and MMP-9 production by prostate cancer cell lines via activation of protease-activated receptors

BACKGROUND. The matrix metalloproteinases (MMP) are a family of proteolytic enzymes involved in facilitating cancer metastasis. Protease-activated receptors (PARs) have previously been shown to be involved in pathways of MMP upregulation by tumor cells. METHODS. Two androgen independent prostate cancer cell lines, PC3 and DU-145, and one androgen dependent prostate cancer line LNCaP, were investigated. PAR expression was detected using RT-PCR and immunofluorochemistry (IFC) techniques. MMP activity assays were used to quantify the levels of MMP-2 and -9 on all three prostate cell lines after PAR activation. RESULTS. RT-PCR and IFC showed the presence of PAR-1 and PAR-2 in all cell lines investigated, only LNCaP showed PAR-3 and PAR-4 expression. Increased levels of MMP-2 and MMP-9 activity, up to sevenfold depending on prostate cancer cell line, following PAR activation by specific PAR peptides was shown. CONCLUSION. Preliminary studies show the activation of PARA or PAR-2 produced increased levels of MMP-2 and MMP-9 activity in prostate cancer cell lines, indicating their potential role in the metastasis of prostate cancer cells. Prostate 60: 168-174, 2004. (C) 2004 Wiley-Liss, Inc.