Exosomal markers

Exosomes are 40-100 nm vesicles that are released from both normal and cancer cells into the extracellular space and can be detected in all biofluids. They are produced from multivesicular intracellular structures and are released by exocytosis, containing in their membrane both general exosomal markers of tetraspanin family (CD9, CD63, CD81), and markers of the parent cell from which they originated. Also their cargo reflects their cell of origin. Exosomes can contain mRNA, microRNAs, tumor antigens, immunomodulatory molecules, and other substances, and they are likely involved in intercellular communication. Analysis of exosomes has both scientific and diagnostic applications.
 

Fig.1: Principle of formation and release of the exosomes.
 
 
For isolation of exosomes, both physical and immunoaffinity methods are being used. Physical methods are based on separation of the vesicles according to their size and involve centrifugation, filtration, size-exclusion chromatography etc.  A disadvantage is that the product can be contaminated by e.g. apoptotic vesicles or lipoproteins. The immunoaffinity methods utilize immunoprecipitating antibodies specific to antigens present in extracellular leaflet of exosomal membrane, attached to immunosorbent particles or to ELISA wells.
 

General exosomal markers:

*Crossreactivity
 
 
Further reading:
 
Yu LL, Zhu J, Liu JX, Jiang F, Ni WK, Qu LS, Ni RZ, Lu CH, Xiao MB: A comparison of traditional and novel methods for the separation of exosomes from human samples. Biomed Res Int. 2018 Jul 26;2018:3634563.
 
Wu SC, Kuo PJ, Rau CS, Wu YC, Wu CJ, Lu TH, Lin CW, Tsai CW, Hsieh CH: Subpopulations of exosomes purified via different exosomal markers carry different microRNA contents. Int J Med Sci. 2021 Jan 1;18(4):1058-1066.
 
Mathieu M, Martin-Jaular L, Lavieu G, Théry C: Specificities of secretion and uptake of exosomes and other extracellular vesicles for cell-to-cell communication. Nat Cell Biol. 2019 Jan;21(1):9-17.
 
Khushman M, Bhardwaj A, Patel GK, Laurini JA, Roveda K, Tan MC, Patton MC, Singh S, Taylor W, Singh AP: Exosomal markers (CD63 and CD9) expression pattern using immunohistochemistry in resected malignant and nonmalignant pancreatic specimens. Pancreas 2017 Jul;46(6):782-788.
 
Cumba Garcia LM, Peterson TE, Cepeda MA, Johnson AJ, Parney IF: Isolation and analysis of plasma-derived exosomes in patients with glioma. Front Oncol. 2019 Jul 16;9:651.
 
Li A, Zhang T, Zheng M, Liu Y, Chen Z: Exosomal proteins as potential markers of tumor diagnosis. J Hematol Oncol. 2017 Dec 27;10(1):175.
 
 
 

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