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Review
. 2021 Dec;40(4):1203-1221.
doi: 10.1007/s10555-021-10014-2. Epub 2021 Dec 27.

The role of the metabolite cargo of extracellular vesicles in tumor progression

Mária Harmati  1 , Mátyás Bukva  1   2   3 , Tímea Böröczky  1   2   3 , Krisztina Buzás  1   2 , Edina Gyukity-Sebestyén  4
Affiliations
Review

The role of the metabolite cargo of extracellular vesicles in tumor progression

Mária Harmati et al. Cancer Metastasis Rev. 2021 Dec.

Abstract

Metabolomic reprogramming in tumor and stroma cells is a hallmark of cancer but understanding its effects on the metabolite composition and function of tumor-derived extracellular vesicles (EVs) is still in its infancy. EVs are membrane-bound sacs with a complex molecular composition secreted by all living cells. They are key mediators of intercellular communication both in normal and pathological conditions and play a crucial role in tumor development. Although lipids are major components of EVs, most of the EV cargo studies have targeted proteins and nucleic acids. The potential of the EV metabolome as a source for biomarker discovery has gained recognition recently, but knowledge on the biological activity of tumor EV metabolites still remains limited. Therefore, we aimed (i) to compile the list of metabolites identified in tumor EVs isolated from either clinical specimens or in vitro samples and (ii) describe their role in tumor progression through literature search and pathway analysis.

Keywords: Cancer; Extracellular vesicles; Metabolites; Metastasis.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Biogenesis and isolation methods of EVs. The left side of the figure shows a schematic overview of the main EV biogenesis pathways. The bottom left of the figure shows how EVs are classified by biogenesis (exosomes and microvesicles) and by size (small and medium/large EVs), indicating the overlap in the size range of the different EV types. The right side of the figure shows the main isolation methods and the comparison of their most important indicators such as yield, and co-isolated contaminants [10, 11]. Abbreviations: ILV, intraluminal vesicle; MVB, multivesicular body; EVs, extracellular vesicles; SN, supernatant; UC, ultracentrifugation; DG-UC, density gradient-ultracentrifugation; SEC, size-exclusion chromatography. This figure was created at BioRender.com
Fig. 2
Fig. 2
Tumor-derived EVs have both local and systemic effects. These EVs can alter the TME, modulate immune responses and prepare distant tissue sites for metastasis. This figure shows some examples of the tumor EV effects. Abbreviation: ECM, extracellular matrix; the figure was created based on [28] at BioRender.com
Fig. 3
Fig. 3
Summary Venn diagram of EV metabolites. The figure summarizes the metabolites identified in the literature according to their source and expression. The top of the figure shows the sources of the EVs investigated in the different studies, and the identified metabolites are shown at the bottom. The different colors and font styles indicate the expression state of metabolites. The figure was created using GIMP
Fig. 4
Fig. 4
A matrix representation of metabolites and their associated pathways. Shades of red indicate the P values, which refers to the significance level of the association with different pathways. The significance increases from left to right of the graph. From top to bottom, the number of pathways associated with a metabolite decreases. The figure was created using RAWGraphs and GIMP
See this image and copyright information in PMC

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