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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 E
D 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+ Tcell
dependent 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

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Exosome and cancer

  • 1. 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 E D 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
  • 2. 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
  • 3. Background and introduction Cell Mol Life Sci 68 (2011) 2667–2688.
  • 4. 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.
  • 5. 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.
  • 6. Biogenesis and release of exosome Raposo G , and Stoorvogel W J Cell Biol 2013;200:373-383
  • 7. 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
  • 8. Composition of exosome Virol. 2011;85:12844-12854
  • 10.  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.
  • 11. 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+ Tcell dependent antitumer effect
  • 12. 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
  • 13. 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.
  • 14. 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)