MP39-11 BLADDER CANCER EXOSOMES CONTAIN TUMOR-ASSOCIATED MRNA AND LONG NON-CODING RNA AND FACILITATE TUMOR PROGRESSION

Abstract

You have accessJournal of UrologyBladder Cancer: Basic Research IV1 Apr 2014MP39-11 BLADDER CANCER EXOSOMES CONTAIN TUMOR-ASSOCIATED MRNA AND LONG NON-CODING RNA AND FACILITATE TUMOR PROGRESSION Jayme Olsen, Jonathan Flax, Edward Messing, and Carla Beckham Jayme OlsenJayme Olsen More articles by this author , Jonathan FlaxJonathan Flax More articles by this author , Edward MessingEdward Messing More articles by this author , and Carla BeckhamCarla Beckham More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.1326AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Exosomes are 30-100nM membrane bound vesicles that contain protein, miRNA, mRNA, long non-coding (lnc) RNA and can facilitate tumor progression. Recently, we showed that exosomes from bladder cancer (BC) cell lines and urine of patients with high-grade BC promote angiogenesis, migration and invasion (submitted). Given the complexity of exosomes, investigation of how each class of biomolecule affects tumor biology is critical. The lncRNAs HOTAIR and MALAT1 have been shown to mediate invasiveness in several tumors including BC. Knockdown of MALAT1 or HOTAIR reduced invasion, growth and motility. To this end, we asked if BC exosomes contain or affect the levels of tumor-associated lncRNAs in cells exposed to exosomes. METHODS A commercial microarray was used to identify mRNA and lncRNAs in exosomes from BC cell lines. qRT-PCR and sequencing confirmed full-length candidate RNAs in exosomes from cell lines and patients. lncRNA and mRNA levels in cells treated with BC exosomes were quantitated by qRT-PCR. Tumor progression of exosome treated cells was evaluated in vitro by standard scratch migration and trans-well invasion assays. RESULTS Over 2000 transcripts were identified in BC exosomes. Candidate transcripts for further analysis were selected based on abundance or known roles in tumor progression and were confirmed by qRT-PCR in exosomes of high-grade BC cell lines: TCC-SUP (grade IV) and T24 (grade III). Some transcripts were more abundant in exosomes vs. corresponding cell lysates. TCC-SUP exosomes were differentially enriched in some transcripts vs. T24 exosomes. Many of the same lncRNAs and mRNAs identified in cell lines, were enriched in urinary exosomes from pT2+ BC patients vs. controls. Exosomes from TCC-SUP, T24 and patients facilitated increased invasion and migration of recipient 5637 BC cells. Importantly, these tumor progression phenotypes correlated with increased levels of lncRNAs including HOTAIR and MALAT1 in recipient 5637cells. Critically, the downstream targets of HOTAIR; laminins, SNAIL and ABL2 involved in epithelial to mesenchymal transition, were also elevated in recipient 5637 cells. CONCLUSIONS BC exosomes from cells lines and urine of pT2+ BC patients contain tumor-associated mRNA and lncRNAs including MALAT1 and HOTAIR and facilitate migration and invasion. Increased levels of several tumor-associated transcripts were observed in exosome treated cells, suggesting that exosomes may deliver and or induce the expression of mRNA and lncRNAs to promote tumor progression. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e429-e430 Peer Review Report Advertisement Copyright & Permissions© 2014MetricsAuthor Information Jayme Olsen More articles by this author Jonathan Flax More articles by this author Edward Messing More articles by this author Carla Beckham More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...