Oncogenic Regulation of Extracellular Vesicle Proteome and Heterogeneity

Mutational and epigenetic driver events profoundly alter intercellular communication pathways in cancer. This effect includes deregulated release, molecular composition, and biological activity of extracellular vesicles (EVs), membranous cellular fragments ranging from a few microns to less than 100...

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Bibliographic Details
Published in:Proteomics (Weinheim) 2019-01, Vol.19 (1-2), p.e1800169-n/a
Main Authors: Choi, Dongsic, Spinelli, Cristiana, Montermini, Laura, Rak, Janusz
Format: Article
Language:English
Subjects:
Animals
Biological activity
Cancer
Cell signaling
Cell Transformation, Neoplastic - genetics
Cell Transformation, Neoplastic - metabolism
Composition
Deregulation
Diagnostic systems
ectosomes
Epithelial-Mesenchymal Transition - genetics
Epithelial-Mesenchymal Transition - physiology
exosomes
Extracellular Vesicles - metabolism
Flow cytometry
Genetic transformation
Heterogeneity
Humans
Invasiveness
Lipids
Mesenchyme
Mutation - genetics
nano flow cytometry
Nucleic acids
oncogenes
Physical properties
Populations
Protein composition
Proteins
Proteome - metabolism
Proteomes
proteomics
Stem cells
subtypes
Technology assessment
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Summary:Mutational and epigenetic driver events profoundly alter intercellular communication pathways in cancer. This effect includes deregulated release, molecular composition, and biological activity of extracellular vesicles (EVs), membranous cellular fragments ranging from a few microns to less than 100 nm in diameter and filled with bioactive molecular cargo (proteins, lipids, and nucleic acids). While EVs are usually classified on the basis of their physical properties and biogenetic mechanisms, recent analyses of their proteome suggest a larger than expected molecular diversity, a notion that is also supported by multicolour nano‐flow cytometry and other emerging technology platforms designed to analyze single EVs. Both protein composition and EV diversity are markedly altered by oncogenic transformation, epithelial to mesenchymal transition, and differentiation of cancer stem cells. Interestingly, only a subset of EVs released from mutant cells may carry oncogenic proteins (e.g., EGFRvIII), hence, these EVs are often referred to as “oncosomes”. Indeed, oncogenic transformation alters the repertoire of EV‐associated proteins, increases the presence of pro‐invasive cargo, and alters the composition of distinct EV populations. Molecular profiling of single EVs may reveal a more intricate effect of transforming events on the architecture of EV populations in cancer and shed new light on their biological role and diagnostic utility.
ISSN:1615-9853
1615-9861
DOI:10.1002/pmic.201800169