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Exosomes Characterization

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Swarnav Mishra
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12 views18 pages

Exosomes Characterization

Uploaded by

Swarnav Mishra
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
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Exosomes Characterization

Guided By: Presented By:


Prof. Bijesh K. Biswal Rajeev Kumar Sahoo
1
Assistant Professor Research Scholar
Department of Life Science Roll No. 520LS1007
Exosomes Characterization

• Biogenesis

• Composition

• Tissue homeostasis

• Recent updates shows role in cancer progression.

2
History

• Discovered in 1983 by Jhonstone et al.

• Lipid Bilayer structure secreted by sheep reticulocytes.

• He named the vesicles “Exosomes” in 1987.

• Initially thought of garbage bag like role to eliminate


unnecessary substances from the cell.

• In 1996, it was reported that exosomes affects other


cells.
3
Origin
• The vesicles secreted by the cell are called Extracellular
vesicles (EVs).

• Based on size and mechanism of formation, EVs are


classified into 3 types: a) Apoptotic bodies
b) Microvesicles (MVs)
c) Exosomes

• Besides these three main subtypes, other EVs include


membrane particles, exosome-like vesicles, neutrophil-
originating EVs (ectosomes), prostate-originating EVs
(prostasomes), migrasomes, oncosomes, large
4
oncosomes
*

5
(Reference from Exosomes in cancer development, metastasis, and immunity by
Lin Zhang and Dihua Yu, 2019)
Apoptotic Bodies

• 1μm or more in diameter

• Contain fragmented nuclei and intracellular organelle

• Apoptotic bodies primarily contain ribosomal RNA


(rRNA)

• Directly formed and released by cell membrane

• Released from apoptotic cells or dying cells. 6

• Mechanism is not well known


Microvesicles (MVs)

• 100 to 1000 nm in diameter

• Contain proteins and nucleic acids

• Microvesicles do not contain any RNA

• Directly formed and released by cell membrane

• Released from healthy cells


7
• Mechanism is not well known
Exosomes
• 50 to 150 nm in diameter

• Contain proteins and nucleic acids

• Exosomes contains large amount of low molecular weight RNA


but not rRNA

• Exosomes are secreted through the endocytosis of the


multivesicular bodies (MVBs).

• Cup shaped

• Types: Lyden and colleagues identified two exosome


8
subpopulations- large exosome vesicles (Exo-L), sized 90–120
nm, and small exosome vesicles (Exo-S), sized 60–80 nm
Biogenesis of Exosomes
• Exosomes originate from the endosome

• The initial endosome is formed by encapsulating the


cell membrane proteins through endocytosis and
intracellular proteins and nucleic acids.

• This initial endosome matures into a late endosome


accompanied by decreasing pH, and multiple ILV
(intraluminal membrane vesicle) are formed inside the
endosome.

• Vesicles containing multiple ILVs are called MVBs, and


the ILVs are released into the extracellular space as 9
MVB fuses with the cell membrane again. These
secreted ILVs are exosomes.
10
(Reference from Exosomes and Their Role in Cancer Progression
By Osaki and Okada, 2019)
Intracellular secretion of Exosomes

• The intracellular formation of ILV has been reported via


two pathways:

a) Endosomal Sorting Complex Required for Transport


(ESCRT) dependent

b) ESCRT independent

11
ESCRT dependent
• Proteins such as ESCRT-0, -I, -II, and -III form complexes
and are involved in a series of ILV formation

ESCRT independent
• Transfer of Exosomes involving ceramide and tetraspanin

• Kosaka and colleagues reported that exosome secretion is

suppressed by inhibition of n-SMase2, an enzyme that

promotes ceramide synthesis.

• Van Niel et al. reported that CD63, a type of tetraspanin, is


12
involved in protein transfer to ILV independent of ESCRT and

ceramide.
Extracellular secretion of Exosomes

• The RAB family proteins help in extracellular release of


exosomes.

• Specially, RAB27A, RAB27B, RAB11, RAB35, and


RAB7, regulate exosome secretion.

• The controlling of exosome secretion by various RAB


proteins is dependent on the cellular context.

• RAB27A and RAB27B control exosome release in HeLa


cells, while RAB7 controls exosome release in MCF-7
breast cancer cells.
13
Exosomes in cancer progression

• Exosome-associated RNAs, miRNAs, proteins, DNAs, and


even metabolites can change the fate of recipient cells by
autocrine and paracrine signaling.
• First, exosomal proteins can change the fate of exosome-
releasing cells themselves via an autocrine pathway
• Second, Exosomal DNA changes cell survival itself. It has
been debated whether exosomes carry DNA, because
exosomes come from MVB in cytoplasm but do not connect
to the nucleus. However, several groups have detected
double-stranded DNA fragments and DNA mutation in
exosomes
• Paracrine signalling-cancer cells can activate the receptors
or change miRNA or RNA expression in the neighboring
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cancer cells to alter their biological phenotypes
Exosomes in cancer progression
• Exosome not only transfer between cancer cells, they also
transfer between cancer cells and stromal cells: stromal
cells accept exosomes derived from cancer cells to
generate a pro-tumor microenvironment; reciprocally,
cancer cells take the exosomes released from stromal cells
to facilitate cancer cell proliferation or invasion.

• Tumor cell–derived exosomes can also regulate endothelial


cell characteristics to promote angiogenesis, especially in
hypoxic conditions

15
Exosomes in cancer drug resistance
• First, exosomes released from tumor cells can help the cells
expel cytotoxic drugs, as has been observed in melanoma
and ovarian cancer.

• Second, drug-sensitive cells become drug resistant by


taking up exosomes derived from drug-resistant cells.

• MiRNAs such as miR-30a, miR-222, or miR-100–5p carried


by exosomes induced drug-sensitive cells to become
resistant possibly through regulating MAPK or mTOR
pathway.

• Third, stromal exosomes can also induce drug resistance in 16


cancer cells
References
• Osaki M, Okada F. Exosomes and their role in cancer
progression. Yonago acta medica. 2019;62(2):182-90.

• Zhang L, Yu D. Exosomes in cancer development,


metastasis, and immunity. Biochimica et Biophysica Acta
(BBA)-Reviews on Cancer. 2019 Apr 1;1871(2):455-68.

• Mashouri L, Yousefi H, Aref AR, Molaei F, Alahari SK.


Exosomes: composition, biogenesis, and mechanisms in
cancer metastasis and drug resistance. Molecular cancer.
2019 Dec;18(1):1-4.

17
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