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Prostate-specific antigen (PSA) and several other members of the kallikrein family of serine proteases are current or potential biomarkers for prostate cancer. Biochemical studies have suggested that the kallikreins may have roles in tumor progression. Therefore, PC3 cell lines stably expressing pre-pro PSA, KLK2 and KLK4 were established to investigate kallikrein functionality in a cellular context. We have previously shown no change in proliferation or invasion through the synthetic extracellular matrix, Matrigel. In contrast, PSA- and KLK4-expressing clones demonstrated a significant increase in migration through microporous membrane barriers compared with parental, vector only and KLK2-expressing cells. In PSA- and KLK4-expressing clones a morphological change towards more irregular, spindle-shaped cells and rearrangement of focal contacts accompanied the increase in migration. Furthermore, the epithelial cell-cell adhesion protein E-cadherin was down-regulated in the PSA- and KLK4-expressing clones while the mesenchymal marker vimentin was up-regulated. These findings suggested that the PSA- and KLK4-expressing clones have undergone an epithelial-mesenchymal transition (EMT)-like transformation. We next compared the gene expression profiles of the transfected and untransfected PC3 cells using Affymetrix microarrays. In addition to the loss of E-cadherin, the expression of a number of other cell-cell and cell-ECM adhesion molecules was reduced in the PSA and KLK4 but not KLK2 clones. These include desmoplakin, junction plakoglobin, claudin-3 and claudin-7 as well as integrin-α2, integrin-β2 and integrin-β4. Further studies are underway to determine the mechanisms underlying these phenotypic changes.

[Proc Amer Assoc Cancer Res, Volume 47, 2006]