You have accessJournal of UrologyProstate Cancer: Basic Research (IV)1 Apr 2013801 REVERSAL OF CHEMOSENSITIVITY AND INDUCTION OF CELL MALIGNANCY OF A NON-MALIGNANT PROSTATE CANCER CELL LINE UPON MICROVESICLE EXPOSURE Sam Cross-Knorr, Joseph Renzulli, Dionysios Pantazatos, Kiki Panagopoulos, Michael Del Tatto, Lisa Goldstein, Peter Quesenberry, and Devasis Chatterjee Sam Cross-KnorrSam Cross-Knorr Providence, RI More articles by this author , Joseph RenzulliJoseph Renzulli Providence, RI More articles by this author , Dionysios PantazatosDionysios Pantazatos Providence, RI More articles by this author , Kiki PanagopoulosKiki Panagopoulos Providence, RI More articles by this author , Michael Del TattoMichael Del Tatto Providence, RI More articles by this author , Lisa GoldsteinLisa Goldstein Providence, RI More articles by this author , Peter QuesenberryPeter Quesenberry Providence, RI More articles by this author , and Devasis ChatterjeeDevasis Chatterjee Providence, RI More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.365AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Microvesicle trafficking is a fundamental cellular process that occurs in cells and is required for multifarious aspects of pathophysiology. A wide variety of microvesicle trafficking genes have been shown to display altered expression in diverse cancers. Moreover, microvesicle trafficking leads to other changes in cellular function, including apoptosis, angiogenesis and proliferation required for increased tumor formation. It has been suggested that the clinical behavior and response of prostate cancer is linked to differences in gene expression. We report several phenotypic changes mediated by microvesicles (MVs) isolated from non- and malignant prostate cells as well as patient biopsied prostate tumor samples. METHODS Human prostate cancer tissue was harvested from fresh specimens and prostate cancer microvesicles were isolated. The microvesicles were then co-cultured with non-malignant cells from a prostate cell line for 21 days. The cells were then harvested and western blot analysis was carried out. RESULTS Microvesicles can reverse the resistance of prostate cancer cells to camptothecin(CPT)chemotherapy. Prostate cells resistant to camptothecin(RC1) undergo apoptosis when co-cultured with MVs isolated from DU145 cells. In addition, we observe the reciprocal effect whereby DU145 cells become resistant to CPT when co-cultured with MVs from RC1 cells. MVs isolated from non-malignant PrEC cells can reverse soft agar colony formation of malignant DU145 cells, with the reciprocal effect also observed. Significantly, we identified an increase in SOCS2 and decrease in STAT3, 2 proteins intimately involved with Jak/STAT signaling, via antibody analysis that may be responsible for the phenotypic changes. Isolation of MVs from 2 Gleason grade 8 prostate cancer patients significantly induced soft agar colony formation of non-malignant PrEC cells. Mass spectrometry analysis of lysates revealed several protein candidates that may be responsible for this phenotypic change. Western blot analysis confirmed the phosphorylation of RKIP, a protein known to lead to enhanced Raf-mediated cell survival signaling and 14-3-3 zeta, a tumor promoting protein. CONCLUSIONS Our study provides a rational basis to investigate proteins and other genetic factors that may be responsible for phenotypic changes that are associated with normal and malignant prostate tissue microvesicles. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e330 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Sam Cross-Knorr Providence, RI More articles by this author Joseph Renzulli Providence, RI More articles by this author Dionysios Pantazatos Providence, RI More articles by this author Kiki Panagopoulos Providence, RI More articles by this author Michael Del Tatto Providence, RI More articles by this author Lisa Goldstein Providence, RI More articles by this author Peter Quesenberry Providence, RI More articles by this author Devasis Chatterjee Providence, RI More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...