Proteomic analysis of exosomes secreted by human mesothelioma cells.
Exosomes are small membrane vesicles secreted into the extracellular compartment by exocytosis. Tumor exosomes may be involved in the sampling of antigens to antigen presenting cells or as decoys allowing the tumor to escape immune-directed destruction. The proteins present in exosomes secreted by tumor cells have been poorly defined. This study describes the protein composition of mesothelioma cell-derived exosomes in more detail. After electrophoresis of exosome preparations, matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) was used to characterize the protein spots. MHC class I was found to be present together with the heat shock proteins HSC70 and HSP90. In addition, we found annexins and PV-1, proteins involved in membrane transport and function. Cytoskeleton proteins and their associated proteins ezrin, moesin, actinin-4, desmoplakin, and fascin were also detected. Besides the molecular motor kinesin-like protein, many enzymes were detected revealing the cytoplasmic orientation of exosomes. Most interesting was the detection of developmental endothelial locus-1 (DEL-1), which can act as a strong angiogenic factor and can increase the vascular development in the neighborhood of the tumor. In conclusion, mesothelioma cells release exosomes that express a discrete set of proteins involved in antigen presentation, signal transduction, migration, and adhesion. Exosomes may play an important role in the interaction between tumor cells and their environment.
Hegmans
Joost P J J
JP
Department of Pulmonary Medicine, Erasmus MC, Rotterdam, The Netherlands. j.hegmans@erasmusmc.nl
Bard
Martin P L
MP
Hemmes
Annabrita
A
Luider
Theo M
TM
Kleijmeer
Monique J
MJ
Prins
Jan-Bas
JB
Zitvogel
Laurence
L
Burgers
Sjaak A
SA
Hoogsteden
Henk C
HC
Lambrecht
Bart N
BN
D000938:Antigen-Presenting Cells / Q000737:chemistry; D015153:Blotting, Western; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D003593:Cytoplasm / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism; D004247:DNA / Q000737:chemistry; D005089:Exocytosis; D005095:Exoribonucleases; D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins / Q000737:chemistry; D018841:HSP90 Heat-Shock Proteins / Q000737:chemistry; D006650:Histocompatibility Testing; D006801:Humans; D007150:Immunohistochemistry; D007621:Karyotyping; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology*; D008654:Mesothelioma / Q000378:metabolism / Q000473:pathology*; D008854:Microscopy, Electron; D011506:Proteins / Q000737:chemistry; D020543:Proteome; D015398:Signal Transduction; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; C494371:HSPA8 protein, human; D011506:Proteins; D020543:Proteome; D004247:DNA; D005095:Exoribonucleases