Tumour-derived Microvesicles Carry Several Surface Determinants and mRNA of Tumour Cells and Transfer Some of These Determinants to Monocytes

Cancer Immunol Immunother. 2006 Jul;55(7):808-18. doi: 10.1007/s00262-005-0075-9. Epub 2005 Nov 9.

Abstract

This study was designed to determine the characteristics of tumour cell-derived microvesicles (TMV) and their interactions with human monocytes. TMV were shed spontaneously by three different human cancer cell lines but their release was significantly increased upon activation of the cells with phorbol 12-myristate 13-acetate (PMA). TMV showed the presence of several surface determinants of tumour cells, e.g. HLA class I, CD29, CD44v7/8, CD51, chemokine receptors (CCR6, CX3CR1), extracellular matrix metalloproteinase inducer (EMMPRIN), epithelial cell adhesion molecule (EpCAM), but their level of expression differed from that on cells they originated from. TMV also carried mRNA for growth factors: vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), interleukin-8 (IL-8) and surface determinants (CD44H). TMV were localized at the monocytes surface following their short exposure to TMV, while at later times intracellularly. TMV transferred CCR6 and CD44v7/8 to monocytes, exerted antiapoptotic effect on monocytes and activated AKT kinase (Protein Kinase B). Thus, TMV interact with monocytes, alter their immunophenotype and biological activity. This implicates the novel mechanism by which tumour infiltrating macrophages may be affected by tumour cells not only by a direct cell to cell contact, soluble factors but also by TMV.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / immunology
  • Adenocarcinoma / ultrastructure
  • Antigens, Neoplasm / analysis
  • Antigens, Neoplasm / immunology*
  • Apoptosis
  • Basigin / genetics
  • Basigin / immunology
  • Cell Line, Tumor / drug effects
  • Cell Line, Tumor / immunology
  • Cell Line, Tumor / ultrastructure
  • Cell Membrane / immunology*
  • Cell Membrane / ultrastructure
  • Cell Survival
  • Chemotaxis
  • Colorectal Neoplasms / immunology
  • Colorectal Neoplasms / ultrastructure
  • Gene Expression Profiling
  • Genes, MHC Class I
  • HLA Antigens / immunology
  • Humans
  • Hyaluronan Receptors / genetics
  • Hyaluronan Receptors / immunology
  • Immunophenotyping
  • Lung Neoplasms / immunology
  • Lung Neoplasms / ultrastructure
  • Membrane Proteins / analysis
  • Membrane Proteins / immunology*
  • Monocytes / immunology*
  • Neoplasm Proteins / analysis
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / immunology*
  • Neoplasms / immunology*
  • Neoplasms / ultrastructure
  • Pancreatic Neoplasms / immunology
  • Pancreatic Neoplasms / ultrastructure
  • Particle Size
  • RNA, Messenger / analysis
  • RNA, Messenger / genetics
  • RNA, Messenger / immunology*
  • Receptors, Chemokine
  • Receptors, Cytokine / genetics
  • Receptors, Cytokine / immunology
  • Tetradecanoylphorbol Acetate / pharmacology

Substances

  • Antigens, Neoplasm
  • BSG protein, human
  • CD44 protein, human
  • HLA Antigens
  • Hyaluronan Receptors
  • Membrane Proteins
  • Neoplasm Proteins
  • RNA, Messenger
  • Receptors, Chemokine
  • Receptors, Cytokine
  • Basigin
  • Tetradecanoylphorbol Acetate