KESHAV RAJ BHUSAL

U N I V E R S I T Y O F O S L O

F A C U L T Y O F M A T H E M A T I C S A N D N A T U R A L S C I E N C ED E P A R T M E N T O F B I O S C I E N C E S

Exosome and Cancer

Background and introduction

Extracellular membrane vesicles(EMV) are phospholipid bilayered vesicles from the eukaryotic cell.

Distinct biogenesis pathways lead to different types of EMV

Exosomes

Shedding microvesicles

Apoptotic blebs(Abs)

communication medium between the cells

Background and introduction

Cell Mol Life Sci 68 (2011) 2667–2688.

Background and introduction

Exosomes are smallest extracellular vesicles.

Size=30–100 nm

originates from late endosomes.

Released in the extracellular medium by a broad array of cells.

First identified in sheep red blood cell ( 1983) -Believed to be a mechanism for the exchange of proteins between cells.

Background and introduction

Believed to be a mechanism for the exchange of proteins between cells.

became interest for immunologists , when they were proposed to play a role in antigen presentation(1996)

finding by Hadi Valadi

exosomes carry mRNA and miRNA,

capacity to vehicle genetic messages.

Biogenesis and release of exosome

Raposo G , and Stoorvogel W J Cell Biol 2013;200:373-383

Biogenesis and release of exosome

Released by

B‐cells,

dendritic cells (DCs),

T‐cells,

epithelial cells,

platelets

present in physiological fluids

serum,

urine,

breast milk,

cerebrospinal fluid,

saliva

Composition of exosome

Virol. 2011;85:12844-12854

Antitumorigenic Role of

Tumor-Derived

Exosomes

Due to their protein and nucleic acids contents, which closely reflects the nature and state of their parental cells, exosomes are considered veritable concentrations of information.

All of the molecules found in exosomes are potentially useful for diagnostic purposes

screening testing,

confirmatory diagnostics,

patient profiling,

monitoring of treatments.

Immunogenic properties

exosomes derived from tumor cells have been shown to have anti-tumorigenic properties

inducing tumor cell apoptosis (Ristorcelli et al., 2008)

enhancing anti-tumor immunity (Zhang et al., 2010)

tumor-derived exosomes have been used as a source of tumor antigens to pulse DCs(Taieb et al., 2006)

Exosome transfer tumer Ag to DC induce CD8+ Tcelldependent antitumer effect

Induction of tumor cell apoptosis

Apoptotic function of tumor-derived exosomes on tumor cells was also reported( Ristorcelli et al, 2008)

human pancreatic tumer cell exosome increase Bax/Decrease Bcl2 expression tumer cell towards mitochondrial apoptotic pathway

Conclusion

Increasing evidence suggests that tumor-derived exosomes can confer anti-tumorigenic effects.

Some evidence also suggest exosomes also have protumerogenic effect.

These controversial effects can be the results of complex interactions between exosomes, responding cells, and environmental factors.

A better understanding of the roles of tumor-derived exosomes in cancer pathogenesis is needed to further improve anti-cancer therapeutics as well as exosome-based cancer diagnostics.

Suggested video on you tube(Documentary by life technologies)

Episode 1- What is exosome(https://www.youtube.com/watch?v=sE2krsErbwI)

Episode2- The history & promise of exosome(https://www.youtube.com/watch?v=Ry9kL-R-7E8)

Episode3- Exosomes in cancer research(https://www.youtube.com/watch?v=SZZ_-fnkEVc)

Episode4- Curiosity and a passion for science(https://www.youtube.com/watch?v=Lsz8sMBxyyM)

Episode5- collaboration,the key to scientific research(https://www.youtube.com/watch?v=-wz90lVQE9w)

Episode6- The next small thing(https://www.youtube.com/watch?v=EB_uI9STq-I)

THANK YOU