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.


CONCLUSIONS
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.
Wilson
Susan R
SR
School of Pharmacy, Medical Biology Centre, Queens University Belfast, 97 Lisburn Road, Belfast, United Kingdom.
Gallagher
Sandra
S
Warpeha
Kate
K
Hawthorne
Susan J
SJ
D000728:Androgens / Q000494:pharmacology; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis*; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis*; D011471:Prostatic Neoplasms / Q000473:pathology*; D044463:Receptor, PAR-1 / Q000502:physiology*; D044464:Receptor, PAR-2 / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D000728:Androgens; D044463:Receptor, PAR-1; D044464:Receptor, PAR-2; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9