685 EPITHELIAL-MESENCYHMAL TRANSITION IN PROSTATE CANCER DISSEMINATED TUMOR CELLS

Abstract

You have accessJournal of UrologyProstate Cancer: Basic Research V1 Apr 2010685 EPITHELIAL-MESENCYHMAL TRANSITION IN PROSTATE CANCER DISSEMINATED TUMOR CELLS Melanie Ketchandji, Theodore Koreckij, Todd Morgan, Colm Morrissey, Paul Lange, Pete Nelson, Ilsa Coleman, Roger Coleman, Marty Kinnunen, Xiaotun Zhang, Bruce Montgomery, and Robert Vessella Melanie KetchandjiMelanie Ketchandji More articles by this author , Theodore KoreckijTheodore Koreckij More articles by this author , Todd MorganTodd Morgan More articles by this author , Colm MorrisseyColm Morrissey More articles by this author , Paul LangePaul Lange More articles by this author , Pete NelsonPete Nelson More articles by this author , Ilsa ColemanIlsa Coleman More articles by this author , Roger ColemanRoger Coleman More articles by this author , Marty KinnunenMarty Kinnunen More articles by this author , Xiaotun ZhangXiaotun Zhang More articles by this author , Bruce MontgomeryBruce Montgomery More articles by this author , and Robert VessellaRobert Vessella More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.1084AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES About 15-30% of patients diagnosed with prostate cancer (PCa) who undergo a radical prostatectomy (RP) later recur. PCa has a proclivity to metastasize to bone. Thus we characterized disseminated tumor cells (DTC) isolated from the bone marrow of PCa patients at various stages of disease progression to gain insight into the events associated with PCa metastases. We observed a loss of the differentiated epithelial phenotype with evidence of epithelial-mesenchymal transition (EMT) in early disease and subsequently mesenchymal-epithelial transition (MET) in advanced disease. METHODS Patients at various stages of disease progression underwent bone marrow aspirations either at the time of surgery or at follow-up. The aspirate was then enriched for epithelial cells using immunomagnetic beads conjugated to antibodies to CD45 and CD61 (negative selection) and to EpCam (positive selection). The enriched cells were stained with a FITC-BerEp4 antibody (anti EpCam) and pools of approximately 10-20 positive cells from 62 patients (33 at RP, 11 with no evidence of disease (NED), and 18 with advanced disease (ADV) were analyzed using cDNA microarrays with real-time PCR confirmation. Human tissue microarrays of fixed paraffin-embedded tissues from forty-four rapid autopsy patients were also used for immunohistochemical (IHC) analyses of EMT-related proteins of interest. RESULTS Gene expression analysis of DTC isolated from the 62 patients revealed a wide range of phenotypic heterogeneity. TWIST-1 (p=<0.001), S100A4 (p=0.002) and SNAIL1 (p=0.012), genes associated with EMT, were differentially expressed between the RP and ADV patients. Differences were also observed between the NED and ADV patients (TWIST-1 (p=0.002) and S100A4 (p=0.05)). Furthermore, IHC revealed that TWIST-1, S100A4 and SNAIL1 were present in PCa bone and soft tissue metastases. Ten of the forty-four RP and NED patients later developed biochemical recurrence. DTC from recurrent patients demonstrated increased expression of TWIST-1 (p=0.003) and decreased expression of E-cadherin (p=0.05) when compared to patients who did not recur. CONCLUSIONS The EMT related genes herein may have an important role in the development of PCa bone metastasis. The expression of E-cadherin and TWIST1 in DTC may predict recurrence in RP and NED patients. The molecular profiles of DTC suggest EMT is an early event in tumor cell dissemination followed by MET as the tumor cells become established within the bone marrow. Interestingly, some, EMT-related proteins continue to be expressed in clinically overt PCa bone metastases. Seattle, WA© 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e267-e268 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information Melanie Ketchandji More articles by this author Theodore Koreckij More articles by this author Todd Morgan More articles by this author Colm Morrissey More articles by this author Paul Lange More articles by this author Pete Nelson More articles by this author Ilsa Coleman More articles by this author Roger Coleman More articles by this author Marty Kinnunen More articles by this author Xiaotun Zhang More articles by this author Bruce Montgomery More articles by this author Robert Vessella More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...