TY - JOUR
T1 - Mitochondrial protein enriched extracellular vesicles discovered in human melanoma tissues can be detected in patient plasma
AU - Jang, Su Chul
AU - Crescitelli, Rossella
AU - Cvjetkovic, Aleksander
AU - Belgrano, Valerio
AU - Olofsson Bagge, Roger
AU - Sundfeldt, Karin
AU - Ochiya, Takahiro
AU - Kalluri, Raghu
AU - Lötvall, Jan
N1 - Funding Information:
This work was funded by the Swedish Research Council (K2014-85X-22504-01-3), VBG Group Herman Krefting Foundation for Asthma and Allergy Research, the Swedish Heart and Lung Foundation (20120528), the Swedish Cancer Foundation (CAN2014/844), and Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education (2016R1A6A3A03007377). We thank Evelin Berger, Annika Thorsell, and Carina Sihlbom at the Proteomics Core Facility, University of Gothenburg, Sweden, for mass spectrometry analysis. The Proteomics Core Facility at Sahlgrenska Academy is grateful to the Inga-Britt and Arne Lundbergs Forskningsstiftlese for the donation of the Orbitrap Fusion Tribrid MS instrument. We thank Bengt R. Johansson for helpful discussions. We also thank Electron Microscopy Unit (EMU), and later, Centre for Cellular Imaging at the University of Gothenburg and the National Microscopy Infrastructure, NMI (VR-RFI 2016-00968) for providing assistance in microscopy. We thank Gunnar Nilsson at the Karolinska Institute, Stockholm, Sweden, and Jonas Nilsson at University of Gothenburg, Gothenburg, Sweden, for the kind gift of the human mast cell line HMC-1 and human melanoma cell line MML1, respectively.
Publisher Copyright:
© 2019, © 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group on behalf of The International Society for Extracellular Vesicles.
PY - 2019
Y1 - 2019
N2 - Extracellular vesicles (EVs), including exosomes and microvesicles, are secreted from all cells, and convey messages between cells in health and disease. However, the diversity of EV subpopulations is only beginning to be explored. Since EVs have been implicated in tumour microenvironmental communication, we started to determine the diversity of EVs specifically in this tissue. To do this, we isolated EVs directly from patient melanoma metastatic tissues. Using EV membrane isolation and mass spectrometry analysis, we discovered enrichment of mitochondrial membrane proteins in the melanoma tissue-derived EVs, compared to non-melanoma-derived EVs. Interestingly, two mitochondrial inner membrane proteins MT-CO2 (encoded by the mitochondrial genome) and COX6c (encoded by the nuclear genome) were highly prevalent in the plasma of melanoma patients, as well as in ovarian and breast cancer patients. Furthermore, this subpopulation of EVs contains active mitochondrial enzymes. In summary, tumour tissues are enriched in EVs with mitochondrial membrane proteins and these mitochondrial membrane proteins can be detected in plasma and are increased in melanoma, ovarian cancer as well as breast cancer.
AB - Extracellular vesicles (EVs), including exosomes and microvesicles, are secreted from all cells, and convey messages between cells in health and disease. However, the diversity of EV subpopulations is only beginning to be explored. Since EVs have been implicated in tumour microenvironmental communication, we started to determine the diversity of EVs specifically in this tissue. To do this, we isolated EVs directly from patient melanoma metastatic tissues. Using EV membrane isolation and mass spectrometry analysis, we discovered enrichment of mitochondrial membrane proteins in the melanoma tissue-derived EVs, compared to non-melanoma-derived EVs. Interestingly, two mitochondrial inner membrane proteins MT-CO2 (encoded by the mitochondrial genome) and COX6c (encoded by the nuclear genome) were highly prevalent in the plasma of melanoma patients, as well as in ovarian and breast cancer patients. Furthermore, this subpopulation of EVs contains active mitochondrial enzymes. In summary, tumour tissues are enriched in EVs with mitochondrial membrane proteins and these mitochondrial membrane proteins can be detected in plasma and are increased in melanoma, ovarian cancer as well as breast cancer.
KW - Extracellular vesicles
KW - melanoma
KW - membrane proteins
KW - mitochondria
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U2 - 10.1080/20013078.2019.1635420
DO - 10.1080/20013078.2019.1635420
M3 - Article
C2 - 31497264
AN - SCOPUS:85071237444
SN - 2001-3078
VL - 8
JO - Journal of Extracellular Vesicles
JF - Journal of Extracellular Vesicles
IS - 1
M1 - 1635420
ER -