title: Thrombomodulin mediates the migratory ability of hormone-independent prostate cancer cells through the regulation of epithelial-to-mesenchymal transition biomarkers.
abstract: Thrombomodulin (TM) is highly expressed in endothelial cells and plays the key role in maintaining physical homeostasis. In addition, many pieces of evidence also show that TM contains the diagnostic value for malignant diseases. TM has been found to correlate with metastatic status in multiple cancers, but its role in prostate cancer progression remains unclear. TM expression was determined in prostate cancer cells (DU-145 and PC-3 cells) using real-time PCR and Western blotting. TM expression was manipulated in prostate cancer cells using TM-specific shRNA and an overexpression system. The proliferation, adhesion, and migratory ability of prostate cancer cells expressing various TM levels were determined using the x'Celligence biosensor system and a transwell migration assay. Higher levels of TM transcription and translation were found in DU-145 cells and were negatively correlated with the low migratory ability of DU-145 cells. After silencing TM expression in DU-145 cells, cell growth decreased, but cell adhesion and migration dramatically increased. TM overexpression in PC-3 cells reduced their metastatic ability. We investigated the possible mechanisms of this phenomenon and determined that the enhanced cell migration was mediated through the expression of E-cadherin and vimentin. TM may be a modulator of hormone-independent prostate cancer (HIPC) metastasis. The downregulation of TM expression enhanced the migratory ability of these cells via an increase in vimentin expression and a decrease in E-cadherin expression.
authors.affiliation: Department of Urology, Chang Gung Memorial Hospital, Keelung, Taiwan.
authors.forename: Chun-Te
authors.initials: CT
authors.lastname: Wu
authors.forename: Yu-Jia
authors.initials: YJ
authors.lastname: Chang
authors.forename: Miao-Fen
authors.initials: MF
authors.lastname: Chen
authors.forename: Jun-Jen
authors.initials: JJ
authors.lastname: Liu
authors.forename: Po-Li
authors.initials: PL
authors.lastname: Wei
authors.forename: Weu
authors.initials: W
authors.lastname: Wang
authors.forename: Hui-Hsiung
authors.initials: HH
authors.lastname: Liu
mesh_terms: D015415:Biomarkers; D015820:Cadherins / Q000032:analysis; D002118:Calcium / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D058750:Epithelial-Mesenchymal Transition; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000473:pathology*; D018180:Thrombomodulin / Q000502:physiology*; D014746:Vimentin / Q000032:analysis
chemical_list: D015415:Biomarkers; D015820:Cadherins; D018180:Thrombomodulin; D014746:Vimentin; D002118:Calcium