Introduction: Prostate cancer (PrCa) is the second leading cause of cancer related death in men worldwide. An emerging area of study is the role played by the extracellular matrix (ECM) in the progression of PrCa, including the role of the ADAMTS family members that are able to cleave key ECM molecules. Of particular interest in this study is ADAMTS-15, a known tumour suppressor and cleavage partner of the ECM component versican (VCAN).
Hypothesis and aims: We hypothesise that ADAMTS-15 acts as tumour suppressor in PrCa via its ability to cleave VCAN. The aims of this study were: (1) to examine the expression and regulation of ADAMTS-15 in PrCa cells, (2) to determine the effect of modulating ADAMTS-15 on PrCa cell proliferation, migration and survival, and (3) to characterise the expression of ADAMTS-15 in PrCa patient biopsies.
Conclusions: Exogenous ADAMTS-15 decreased cell migration of PC-3 PrCa cells. Furthermore stable expression of ADAMTS-15 in PC-3 and LNCaP cells led to significant down-regulation of migration and proliferation, with an increase in apoptosis. In patient biopsies ADAMTS-15 was predominantly localised to the stroma in benign prostatic hyperplasia, and in both stromal and glandular epithelial in low and high grade PrCa. Co-expression of VCAN and ADAMTS-15 was also identified in the secretory and basal cells in Gleason Grade 7 PrCa patient specimens. Our data suggests ADAMTS-15 is expressed in PrCa and can inhibit cell proliferation and cell migration, as well as induce apoptosis. Further studies are required to investigate the functions of ADAMTS-15 and VCAN in PrCa progression.