Exosomes of invasive urothelial carcinoma cells are characterized by a specific miRNA expression signature
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Sophie Baumgart1, Sebastian Hölters1, Carsten-Henning Ohlmann1, Rainer Bohle2, Michael Stöckle1, Marie Stampe Ostenfeld3, Lars Dyrskjøt3, Kerstin Junker1 and Joana Heinzelmann1
1Department of Urology and Pediatric Urology, Saarland University Medical Center, 66424 Homburg, Germany
2Institute of Pathology, Saarland University Medical Center, 66424 Homburg, Germany
3Department of Molecular Medicine, Aarhus University Hospital, 8200 Aarhus, Denmark
Sophie Baumgart, email: Sophie.email@example.com
Keywords: exosomes, miRNAs, bladder cancer, exosomal miRNA, tumorigenesis
Received: October 26, 2016 Accepted: April 20, 2017 Published: May 04, 2017
Muscle-invasive bladder cancer (MIBC) represents a highly aggressive tumor type compared to non-muscle-invasive tumors. MIBC is characterized by specific molecular alterations, which may also modulate extracellular tumorigenic effects. Tumor-associated exosomes, especially exosomal miRNAs, are important regulators in the interaction between tumor cells and tumor microenvironment by affecting tumor-promoting processes in target cells. It is important to analyze whether their exosomal patterns also reflect the specific molecular characteristics of MIBC. The aim of this study was to compare the miRNA expression in secreted exosomes from urinary bladder cancer cells (UBC) with different degrees of invasiveness. By electron microscopy, nanotracking analysis and western blot we proofed a high quality of isolated exosomes. Microarray analysis identified an invasion-associated signature of 15 miRNAs, which is significantly altered in exosomes of invasive UBC compared to non-invasive counterparts. Therefrom, 9 miRNAs are consistent differently expressed in both, invasive cells and their secreted exosomes. The remaining 6 exosome-specific miRNAs are only deregulated in exosomes but not in their parental cells. MiRNA alterations were verified by qPCR in cell culture and urinary exosomes. In conclusion, we showed that exosomes from invasive UBC cells are characterized by a specific miRNA signature. Further analyses have to clarify the functional relevance of exosomal miRNAs secreted by invasive bladder cancer cells for modification of the tumor microenvironment and their putative role as molecular markers in liquid biopsies.
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