Quantitative Localized Analysis Reveals Distinct Exosomal Protein-Specific Glycosignatures: Implications in Cancer Cell Subtyping, Exosome Biogenesis, and Function.
J Am Chem Soc
; 142(16): 7404-7412, 2020 04 22.
Article
em En
| MEDLINE
| ID: mdl-32239931
ABSTRACT
Protein-specific glycoform analysis is essential for the thorough understanding of cellular chemistry and signaling but presents a significant assay challenge for small-sized, free-floating exosomes, ubiquitous regulators of cellular physiological functions and mediators of intercellular communication. We report herein a quantitative localized analysis (QLA) method for the first-time achievement of a protein-specific glycosignature assay on these important extracellular vesicles. The integration of localized chemical remodeling and quantitative electrochemistry allows the proof-of-concept QLA examination of exosomal mucin 1 (MUC1)-specific terminal galactose/N-acetylgalactosamine (Gal/GalNAc). In combination with sialic acid (Sia) cleavage manipulation for the exposure of originally capped Gal/GalNAc, QLA has revealed distinct MUC1-specific sialylation capping ratios for MCF-7 and MDA-MB-231 exosomes, as well as when compared to parent cells. These findings suggest a useful noninvasive indicator for subtyping cancer cells and exosome secretion as a likely venue for the preservation of cellular compositional and functional integrity. The QLA method also permits dynamic monitoring of changes in the exosomal MUC1-specific sialylation capping ratio, enabling the distinction of biogenesis pathways of exosomes.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Exossomos
/
Vesículas Extracelulares
/
Neoplasias
Limite:
Humans
Idioma:
En
Revista:
J Am Chem Soc
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
China