title: Altered expression of epithelial-to-mesenchymal transition proteins in extraprostatic prostate cancer.
abstract: Epithelial to mesenchymal transition (EMT) of cancer cells involves loss of epithelial polarity and adhesiveness, and gain of invasive and migratory mesenchymal behaviours. EMT occurs in prostate cancer (PCa) but it is unknown whether this is in specific areas of primary tumours. We examined whether any of eleven EMT-related proteins have altered expression or subcellular localisation within the extraprostatic extension component of locally advanced PCa compared with other localisations, and whether similar changes may occur in in vitro organotypic PCa cell cultures and in vivo PCa models. Expression profiles of three proteins (E-cadherin, Snail, and α-smooth muscle actin) were significantly different in extraprostatic extension PCa compared with intra-prostatic tumour, and 18/27 cases had an expression change of at least one of these three proteins. Of the three significantly altered EMT proteins in pT3 samples, one showed similar significantly altered expression patterns in in vitro organotypic culture models, and two in in vivo Pten-/- model samples. These results suggest that changes in EMT protein expression can be observed in the extraprostatic extension component of locally invasive PCa. The biology of some of these changes in protein expression may be studied in certain in vitro and in vivo PCa models.
authors.affiliation: Department of Cellular Pathology, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Headington, Oxford, UK.|Nuffield Department of Surgical Sciences, University of Oxford, Headington, Oxford, UK.
authors.forename: Clare
authors.initials: C
authors.lastname: Verrill
authors.affiliation: Nuffield Department of Surgical Sciences, University of Oxford, Headington, Oxford, UK.
authors.forename: Lucia
authors.initials: L
authors.lastname: Cerundolo
authors.affiliation: CRUK/MRC Oxford Institute for Radiation Oncology, University of Oxford, Headington, Oxford, UK.
authors.forename: Chad
authors.initials: C
authors.lastname: Mckee
authors.affiliation: Ludwig Institute for Cancer Research Ltd, University of Oxford, Nuffield Department of Clinical Medicine, Headington, Oxford, UK.
authors.forename: Michael
authors.initials: M
authors.lastname: White
authors.affiliation: Department of Oncology, University of Oxford, Headington, Oxford, UK.
authors.forename: Christiana
authors.initials: C
authors.lastname: Kartsonaki
authors.affiliation: Department of Cellular Pathology, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Headington, Oxford, UK.
authors.forename: Eve
authors.initials: E
authors.lastname: Fryer
authors.affiliation: Nuffield Department of Surgical Sciences, University of Oxford, Headington, Oxford, UK.|Ludwig Institute for Cancer Research Ltd, University of Oxford, Nuffield Department of Clinical Medicine, Headington, Oxford, UK.
authors.forename: Emma
authors.initials: E
authors.lastname: Morris
authors.affiliation: Department of Urology, Churchill Hospital, Headington, Oxford, UK.
authors.forename: Simon
authors.initials: S
authors.lastname: Brewster
authors.affiliation: Ludwig Institute for Cancer Research Ltd, University of Oxford, Nuffield Department of Clinical Medicine, Headington, Oxford, UK.
authors.forename: Indrika
authors.initials: I
authors.lastname: Ratnayaka
authors.affiliation: Nuffield Department of Surgical Sciences, University of Oxford, Headington, Oxford, UK.
authors.forename: Luke
authors.initials: L
authors.lastname: Marsden
authors.affiliation: Nuffield Department of Surgical Sciences, University of Oxford, Headington, Oxford, UK.|Departments of Surgery (Urology Service), Laboratory Medicine (Clinical Chemistry Service) and Medicine (Genitourinary Oncology Service), Memorial Sloan Kettering Cancer Center, New York, NY, USA.|Department of Laboratory Medicine and Clinical Sciences in Malmö, Lund University, Skåne University Hospital, Malmö, Sweden.|Institute of Biomedical Technology, University of Tampere, Tampere, Finland.
authors.forename: Hans
authors.initials: H
authors.lastname: Lilja
authors.affiliation: CRUK/MRC Oxford Institute for Radiation Oncology, University of Oxford, Headington, Oxford, UK.
authors.forename: Ruth
authors.initials: R
authors.lastname: Muschel
authors.affiliation: Ludwig Institute for Cancer Research Ltd, University of Oxford, Nuffield Department of Clinical Medicine, Headington, Oxford, UK.
authors.forename: Xin
authors.initials: X
authors.lastname: Lu
authors.affiliation: Nuffield Department of Surgical Sciences, University of Oxford, Headington, Oxford, UK.
authors.forename: Freddie
authors.initials: F
authors.lastname: Hamdy
authors.affiliation: Nuffield Department of Surgical Sciences, University of Oxford, Headington, Oxford, UK.|Ludwig Institute for Cancer Research Ltd, University of Oxford, Nuffield Department of Clinical Medicine, Headington, Oxford, UK.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Bryant
mesh_terms: D000199:Actins / Q000096:biosynthesis*; D000368:Aged; D000818:Animals; D015820:Cadherins / Q000096:biosynthesis*; D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D018345:Mice, Knockout; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D000071250:Snail Family Transcription Factors / Q000096:biosynthesis*; D046888:Tissue Array Analysis
chemical_list: C541116:ACTA2 protein, human; D000199:Actins; D015820:Cadherins; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors
keywords: Pathology Section; epithelial to mesenchymal transition; extraprostatic prostate cancer; immunohistochemistry; in vitro organotypic cell culture; in vivo mouse prostate cancer model