Prostate Transglutaminase (TGase-4) Induces Epithelial-to-Mesenchymal Transition in Prostate Cancer Cells

More men die with prostate cancer (PCa) than from it. However, once PCa is no longer organ-confined, it is associated with significant mortality. Epithelial-to-mesenchymal transition (EMT) is one mechanism facilitating progression in cancer. Our studies of transglutaminase-4 (TGase-4), a member of the TGase family, expressed in the prostate gland, have implicated it in the regulation of the invasive properties of PCa. The present study investigated the role of TGase-4 on EMT of PCa cells. Materials and Methods: A panel of PCa cell lines: CA-HPV-10, PZ-HPV-7, PC-3 and DU-145 were used. An anti-TGase-4 transgene was constructed to eliminate the expression of TGase-4 in CA-HPV-10 (positive for TGase-4). An expression construct for human TGase-4 was used to transfect PCa cells negative for TGase-4. The pattern of E-cadherin, N-cadherin and vimentin in these cells were evaluated using immunofluorescent staining. Cell motility was assessed using scratch wounding and ekectric cell-substrate impedance sensing (ECIS) assays. Results: Treatment of PZ-HPV-7 and CA-HPV10 cells with rhTGase-4 resulted in a significant increase in cell migration (1,407.9 Omega +/- 6.4 Omega vs. 1,691.2 Omega +/- 8.3 Omega in non-treated and rhTGase-4 treated cells, respectively, p < 0.01). Cells strongly expressing E-cadherin showed substantial changes of E-cadherin staining in that, after treatment with TGase-4, the intercellular staining of E-cadherin was diminished. Concomitantly, there was acquisition of N-cadherin in TGase4- treated cells. Elimination of TGase-4 from CA-HPV-10 cells