RT Journal Article
SR Electronic
T1 A subgroup of mitochondrial extracellular vesicles discovered in human melanoma tissues are detectable in patient blood
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 174193
DO 10.1101/174193
A1 Su Chul Jang
A1 Rossella Crescitelli
A1 Aleksander Cvjetkovic
A1 Valerio Belgrano
A1 Roger Olofsson Bagge
A1 Johanna L. Höög
A1 Karin Sundfeldt
A1 Takahiro Ochiya
A1 Raghu Kalluri
A1 Jan Lötvall
YR 2017
UL http://biorxiv.org/content/early/2017/08/09/174193.abstract
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 are only beginning to be explored. Since EVs have been implicated in tumor 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. Specifically, EVs positive for a combination of the two mitochondrial inner membrane proteins MT-CO2 (mitochondrial genome) and COX6c (nuclear genome) were detected in the plasma of melanoma patients, and in ovarian and breast cancer patients. Furthermore, this subpopulation of EVs, contains active mitochondrial enzymes. Our findings show that tumor tissues are enriched in EVs with mitochondrial proteins and enzymatic activity, and these EVs can be detected in blood.