Investigating the impact of prostate cancer exosomal microRNA on cancer stroma formation. — The Association Specialists
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Investigating the impact of prostate cancer exosomal microRNA on cancer stroma formation. (443)

Samuel E Brennan 1 , Nham Tran 2 3 , Aled Clayton 4 , Eileen M McGowan 1 , Paul J Cozzi 5
  1. Translational Cancer Research Group, School of Medical and Molecular Biosciences, Faculty of Science, University of Technology, Sydney, Ultimo, NSW, Australia
  2. Centre for Health Technologies, University of Technology, Sydney, Ultimo, NSW, Australia
  3. Faculty of Engineering and Information Technology, University of Technology, Sydney, Ultimo, NSW, Australia
  4. Velindre Cancer Centre, Cardiff University, Cardiff, Wales, UK
  5. Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia

Background:  The UTS Translational Cancer Research Group is investigating the utility of circulating microRNA enriched prostate cancer (PCa) nanovesicles (40-100nm) to develop novel non-invasive biomarker tests for early PCa diagnosis and prognosis. Exosomes contain and deliver protein, DNA and RNA which may influence the function of other cells in the body.  Over the last two years, interest in exosomes has grown exponentially with respect to their potential use as cancer diagnostics and understanding their role in cancer development and progression.  Recent reports have shown that PCa exosomes cause differentiation of fibroblasts into myofibroblasts, a common feature of PCa stromal tissue.

 Aims: To identify microRNAs with potentially important functions in the PCa microenvironment and to test their ability to influence fibroblast gene expression.

 Methods: MicroRNAs up-regulated in prostate epithelium and PCa cell line derived exosomes were identified by microarray analysis. MicroRNAs that were highly expressed were selected for validation using androgen independent PCa cell line DU145 exosomes. Primary fibroblast cells were exposed to DU145 exosomes for 8, 27 and 72 hours prior to RNA extraction. Quantitative real-time PCR was performed to ascertain the levels of these microRNAs, as well as their predicted target genes in fibroblasts.  Fluorescence microscopy was used to visualise alpha-SMA protein expression; a marker of myofibroblastic differentiation.

 Results: DU145 exosome treatment of fibroblasts caused them to differentiate into myofibroblasts. However, the exosomal microRNAs of interest did not play a role in this differentiation process.

 Conclusions: DU145 PCa exosomes directly influence the phenotype of fibroblast cells. However, the lack of exosomal microRNA involvement in this process was unexpected given the torrent of recent publications on exosome function. Many cell types make up the cancer stroma including epithelial cells and mesenchymal stem cells. The possibility that exosomal microRNA may influence these cells requires further exploration.