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Proximity Proteomics Has Potential for Extracellular Vesicle Identification
journal contribution
posted on 2021-06-11, 20:47 authored by Hisako Kaneda, Yui Ida, Ryusuke Kuwahara, Izumi Sato, Takanari Nakano, Haruhiko Tokuda, Tsuyoshi Sato, Takayuki Murakoshi, Koichi Honke, Norihiro KotaniExtracellular vesicles (EVs) are
biomarkers and mediators of intercellular
communication. In biological samples, EVs are secreted by various
types of cells. The proteomic identification of proteins expressed
in EVs has potential to contribute to research and clinical applications,
particularly for cancer. In this study, the proximity-labeling method-based
proteomic approach was used for EV identification, labeling membrane
components proximal to a given molecule on the EV membrane surface.
Due to the small labeling range, proteins on the surface of the same
EVs are likely to be labeled by selecting a given EV surface antigen.
The protein group of cancer cell-secreted EV (cEV), which abundantly
expresses a close homologue of L1 (CHL1), was examined using a model
mouse for lung cancer (LC). cEV-expressed proteins were identified
by proteomic analysis of enzyme-mediated activation of radical sources
by comparing serum EVs from wild-type and LC mice. SLC4A1 was found
to be co-expressed in CHL1-expressing EVs, highlighting EVs expressing
both CHL1 and SLC4A1 as candidates for cEVs. Serum EVs expressing
both CHL1 and caspase 14 were significantly elevated in LC patients
compared with healthy individuals. Thus, the combination of proximity
labeling and proteomic analysis allows for effective EV identification.