Mass-Spectrometry-Based Molecular Characterization of Extracellular Vesicles: Lipidomics and Proteomics

被引:209
作者
Kreimer, Simion [1 ,2 ]
Belov, Arseniy M. [1 ,2 ]
Ghiran, Ionita [4 ]
Murthy, Shashi K. [1 ,3 ]
Frank, David A. [5 ,6 ,7 ]
Ivanov, Alexander R. [1 ,2 ]
机构
[1] Northeastern Univ, Barnett Inst Chem & Biol Anal, Boston, MA 02115 USA
[2] Northeastern Univ, Dept Chem & Chem Biol, Boston, MA 02115 USA
[3] Northeastern Univ, Dept Chem Engn, Boston, MA 02115 USA
[4] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA
[5] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA
[6] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA
[7] Harvard Univ, Sch Med, Boston, MA 02115 USA
关键词
extracellular vesicle; EV; exosome; microvesicle; microparticle; molecular profiling; mass spectrometry; proteomics; lipidomics; post-translational modifications; CELL-DERIVED EXOSOMES; BLUE NATIVE ELECTROPHORESIS; MEMBRANE-PROTEIN COMPLEXES; QUANTITATIVE PROTEOMICS; N-GLYCOSYLATION; PRION PROTEIN; HUMAN PLASMA; CLASS-II; MICROVESICLES; IDENTIFICATION;
D O I
10.1021/pr501279t
中图分类号
Q5 [生物化学];
学科分类号
070307 [化学生物学];
摘要
This review discusses extracellular vesicles (EVs), which are submicron-scale, anuclear, phospholipid bilayer membrane enclosed vesicles that contain lipids, metabolites, proteins, and RNA (micro and messenger). They are shed from many, if not all, cell types and are present in biological fluids and conditioned cell culture media. The term EV, as coined by the International Society of Extracellular Vesicles (ISEV), encompasses exosomes (30-100 nm in diameter), microparticles (100-1000 nm), apoptotic blebs, and other EV subsets. EVs have been implicated in cell cell communication, coagulation, inflammation, immune response modulation, and disease progression. Multiple studies report that EV secretion from disease-affected cells contributes to disease progression, e.g., tumor niche formation and cancer metastasis. EVs are attractive sources of biomarkers due to their biological relevance and relatively noninvasive accessibility from a range of physiological fluids. This review is focused on the molecular profiling of the protein and lipid constituents of EVs, with emphasis on mass-spectrometry-based "omic" analytical techniques. The challenges in the purification and molecular characterization of EVs, including contamination of isolates and limitations in sample quantities, are discussed along with possible solutions. Finally, the review discusses the limited but growing investigation of post-translational modifications of EV proteins and potential strategies for future in-depth molecular characterization of EVs.
引用
收藏
页码:2367 / 2384
页数:18
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