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Subtypes of tumour cell-derived small extracellular vesicles having differently externalized phosphatidylserine.

Authors
  • Matsumura, Sachiko1
  • Minamisawa, Tamiko1
  • Suga, Kanako1
  • Kishita, Hiromi2
  • Akagi, Takanori2
  • Ichiki, Takanori2
  • Ichikawa, Yuki3
  • Shiba, Kiyotaka1
  • 1 Division of Protein Engineering, Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan. , (Japan)
  • 2 Department of Material Engineering, School of Engineering, The University of Tokyo, Tokyo, Japan. , (Japan)
  • 3 IMRA America, Inc., Ann Arbor, MI, USA.
Type
Published Article
Journal
Journal of Extracellular Vesicles
Publisher
Informa UK (Taylor & Francis)
Publication Date
Jan 01, 2019
Volume
8
Issue
1
Pages
1579541–1579541
Identifiers
DOI: 10.1080/20013078.2019.1579541
PMID: 30834072
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Phosphatidylserine (PS) has skewed distributions in the plasma membrane and is preferentially located in the inner leaflet of normal cells. Tumour cells, however, expose PS at the outer leaflet of cell surfaces, thereby potentially modulating the bio-signalling of cells. Interestingly, exosomes - or, more properly, small extracellular vesicles (sEVs) - which are secreted from tumour cells, are enriched with externalized PS, have been proposed as being involved in the progression of cancers, and could be used as a marker for tumour diagnostics. However, the sEV fractions prepared from various methods are composed of different subtypes of vesicles, and knowledge about the subtypes enriched with exposed PS is still limited. Here, we differentiated sEVs from cancer cell lines by density gradient centrifugation and characterized the separated fractions by using gold-labelling of PS in atomic force microscopy, thrombin generation assay, size and zeta potential measurements, and western blot analysis. These analyses revealed a previously unreported PS+-enriched sEV subtype, which is characterized by a lower density than that of canonical exosomes (1.06 g/ml vs. 1.08 g/ml), larger size (122 nm vs. 105 nm), more negative zeta potential (-28 mV vs. -21 mV), and lower abundance of canonical exosomal markers. The identification of the PS-exposed subtype of sEVs will provide deeper insight into the role of EVs in tumour biology and enhance the development of EV-based tumour diagnosis and therapy.

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