title: A novel spontaneous model of epithelial-mesenchymal transition (EMT) using a primary prostate cancer derived cell line demonstrating distinct stem-like characteristics.
abstract: Cells acquire the invasive and migratory properties necessary for the invasion-metastasis cascade and the establishment of aggressive, metastatic disease by reactivating a latent embryonic programme: epithelial-to-mesenchymal transition (EMT). Herein, we report the development of a new, spontaneous model of EMT which involves four phenotypically distinct clones derived from a primary tumour-derived human prostate cancer cell line (OPCT-1), and its use to explore relationships between EMT and the generation of cancer stem cells (CSCs) in prostate cancer. Expression of epithelial (E-cadherin) and mesenchymal markers (vimentin, fibronectin) revealed that two of the four clones were incapable of spontaneously activating EMT, whereas the others contained large populations of EMT-derived, vimentin-positive cells having spindle-like morphology. One of the two EMT-positive clones exhibited aggressive and stem cell-like characteristics, whereas the other was non-aggressive and showed no stem cell phenotype. One of the two EMT-negative clones exhibited aggressive stem cell-like properties, whereas the other was the least aggressive of all clones. These findings demonstrate the existence of distinct, aggressive CSC-like populations in prostate cancer, but, importantly, that not all cells having a potential for EMT exhibit stem cell-like properties. This unique model can be used to further interrogate the biology of EMT in prostate cancer.
authors.affiliation: John van Geest Cancer Research Centre, Nottingham Trent University, Nottingham, NG11 8NS, UK.
authors.forename: Naomi
authors.initials: N
authors.lastname: Harner-Foreman
authors.affiliation: John van Geest Cancer Research Centre, Nottingham Trent University, Nottingham, NG11 8NS, UK.
authors.forename: Jayakumar
authors.initials: J
authors.lastname: Vadakekolathu
authors.affiliation: John van Geest Cancer Research Centre, Nottingham Trent University, Nottingham, NG11 8NS, UK.
authors.forename: Stéphanie A
authors.initials: SA
authors.lastname: Laversin
authors.affiliation: John van Geest Cancer Research Centre, Nottingham Trent University, Nottingham, NG11 8NS, UK.
authors.forename: Morgan G
authors.initials: MG
authors.lastname: Mathieu
authors.affiliation: John van Geest Cancer Research Centre, Nottingham Trent University, Nottingham, NG11 8NS, UK.
authors.forename: Stephen
authors.initials: S
authors.lastname: Reeder
authors.affiliation: John van Geest Cancer Research Centre, Nottingham Trent University, Nottingham, NG11 8NS, UK.
authors.forename: A Graham
authors.initials: AG
authors.lastname: Pockley
authors.affiliation: John van Geest Cancer Research Centre, Nottingham Trent University, Nottingham, NG11 8NS, UK.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Rees
authors.affiliation: John van Geest Cancer Research Centre, Nottingham Trent University, Nottingham, NG11 8NS, UK.
authors.forename: David J
authors.initials: DJ
authors.lastname: Boocock
mesh_terms: D015415:Biomarkers; D015820:Cadherins / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D019008:Drug Resistance, Neoplasm; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects / Q000235:genetics; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D059467:Transcriptome; D014746:Vimentin / Q000378:metabolism
chemical_list: D015415:Biomarkers; D015820:Cadherins; D014746:Vimentin