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 PAR‐1 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. © 2004 Wiley‐Liss, Inc.