Exosome and Cancer KESHAV RAJ BHUSAL UNIVERSITY OF
Exosome and Cancer KESHAV RAJ BHUSAL UNIVERSITY OF OSLO FACULTY OF MATHEMATICS AND NATURAL SCIENCE DEPARTMENT OF BIOSCIENCES
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 m. RNA and mi. RNA, 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 CD 8+ 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 Bcl 2 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 exosomebased cancer diagnostics.
Suggested video on you tube (Documentary by life technologies) �Episode 1 - What is exosome (https: //www. youtube. com/watch? v=s. E 2 krs. Erbw. I) �Episode 2 - The history & promise of exosome (https: //www. youtube. com/watch? v=Ry 9 k. L-R-7 E 8) �Episode 3 - Exosomes in cancer research (https: //www. youtube. com/watch? v=SZZ_-fnk. EVc) �Episode 4 - Curiosity and a passion for science (https: //www. youtube. com/watch? v=Lsz 8 s. MBxyy. M) �Episode 5 - collaboration, the key to scientific research (https: //www. youtube. com/watch? v=-wz 90 l. VQE 9 w) �Episode 6 - The next small thing (https: //www. youtube. com/watch? v=EB_u. I 9 STq-I)
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