Identification and characterization of proteins isolated from microvesicles derived from human lung cancer pleural effusions

Proteomics. 2013 Jul;13(14):2125-34. doi: 10.1002/pmic.201200323.

Abstract

Microvesicles (MVs, also known as exosomes, ectosomes, microparticles) are released by various cancer cells, including lung, colorectal, and prostate carcinoma cells. MVs released from tumor cells and other sources accumulate in the circulation and in pleural effusion. Although recent studies have shown that MVs play multiple roles in tumor progression, the potential pathological roles of MV in pleural effusion, and their protein composition, are still unknown. In this study, we report the first global proteomic analysis of highly purified MVs derived from human nonsmall cell lung cancer (NSCLC) pleural effusion. Using nano-LC-MS/MS following 1D SDS-PAGE separation, we identified a total of 912 MV proteins with high confidence. Three independent experiments on three patients showed that MV proteins from PE were distinct from MV obtained from other malignancies. Bioinformatics analyses of the MS data identified pathologically relevant proteins and potential diagnostic makers for NSCLC, including lung-enriched surface antigens and proteins related to epidermal growth factor receptor signaling. These findings provide new insight into the diverse functions of MVs in cancer progression and will aid in the development of novel diagnostic tools for NSCLC.

Keywords: Cell biology; Exosome; Microvesicle; Nonsmall cell lung cancer; Pleural effusion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Carcinoma, Non-Small-Cell Lung / chemistry*
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Chromatography, Liquid
  • Databases, Protein
  • ErbB Receptors / metabolism
  • Exosomes / chemistry*
  • Exosomes / metabolism
  • Female
  • Humans
  • Lung / chemistry
  • Lung Neoplasms / chemistry*
  • Lung Neoplasms / metabolism
  • Male
  • Microscopy, Electron
  • Neoplasm Proteins / analysis*
  • Neoplasm Proteins / chemistry
  • Neoplasm Proteins / classification
  • Pleural Effusion / metabolism*
  • Proteome / analysis
  • Proteome / chemistry
  • Proteomics
  • Reproducibility of Results
  • Signal Transduction
  • Tandem Mass Spectrometry

Substances

  • Neoplasm Proteins
  • Proteome
  • EGFR protein, human
  • ErbB Receptors