Identifying mRNA, microRNA and protein profiles of melanoma exosomes

PLoS One. 2012;7(10):e46874. doi: 10.1371/journal.pone.0046874. Epub 2012 Oct 9.

Abstract

Background: Exosomes are small membranous vesicles secreted into body fluids by multiple cell types, including tumor cells, and in various disease conditions. Tumor exosomes contain intact and functional mRNAs, small RNAs (including miRNAs), and proteins that can alter the cellular environment to favor tumor growth. Molecular profiling may increase our understanding of the role of exosomes in melanoma progression and may lead to discovery of useful biomarkers.

Methodology/principal findings: In the present study, we used mRNA array profiling to identify thousands of exosomal mRNAs associated with melanoma progression and metastasis. Similarly, miRNA array profiling identified specific miRNAs, such as hsa-miR-31, -185, and -34b, involved in melanoma invasion. We also used proteomic analysis and discovered differentially expressed melanoma exosomal proteins, including HAPLN1, GRP78, syntenin-1, annexin A1, and annexin A2. Importantly, normal melanocytes acquired invasion ability through molecules transported in melanoma cell-derived exosomes.

Conclusions/significance: Our results indicate that melanoma-derived exosomes have unique gene expression signatures, miRNA and proteomics profiles compared to exosomes from normal melanocytes. To the best of our knowledge, this is the first in-depth screening of the whole transcriptome/miRNome/proteome expression in melanoma exosomes. These results provide a starting point for future more in-depth studies of tumor-derived melanoma exosomes, which will aid our understanding of melanoma biogenesis and new drug-targets that may be translated into clinical applications, or as non-invasive biomarkers for melanoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Disease Progression
  • Exosomes / metabolism*
  • Extracellular Space / metabolism
  • Gene Expression Profiling*
  • Humans
  • Melanocytes / cytology
  • Melanocytes / pathology
  • Melanoma / genetics
  • Melanoma / metabolism
  • Melanoma / pathology*
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism*
  • Neoplasm Invasiveness
  • Oligonucleotide Array Sequence Analysis
  • Proteomics*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Signal Transduction / genetics

Substances

  • MicroRNAs
  • RNA, Messenger

Grant support

This work was supported by University of Louisville School of Medicine Collaborative Matching Grant (H. Hao), University of Louisville Clinical and Translational Science Pilot Grant program Innovative Award (K. McMasters), and Melanoma Research Foundation Established Investigator Award (K. McMasters). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.