Carcinogenic XXXX Secretes Extracellular Vesicles That Promote Cholangiocytes to Adopt a Tumorigenic Phenotype.

@entity1 @entity32 @entity5 @entity281 @entity201 @entity8072
BACKGROUND:    Throughout Asia, there is an unprecedented link between @entity201 and @entity281 with the @entity8072 Opisthorchis viverrini. Multiple processes, including chronic @entity32 and secretion of parasite proteins into the biliary epithelium, @entity5 . Until now, the mechanism and effects of parasite protein entry into cholangiocytes was unknown. METHODS:    Various microscopy techniques were used to identify O. viverrini extracellular vesicles (EVs) and their internalization by @entity1 cholangiocytes. Using mass spectrometry we characterized the EV proteome and associated changes in cholangiocytes after EV uptake, and we detected EV proteins in bile of infected hamsters and @entity1 . Cholangiocyte proliferation and interleukin 6 (IL-6) secretion was measured to assess the impact of EV internalization. RESULTS:    EVs were identified in fluke culture medium and bile specimens from infected hosts. EVs internalized by cholangiocytes drove cell proliferation and IL-6 secretion and induced changes in protein expression associated with endocytosis, wound repair, and @entity5 . Antibodies to an O. viverrini tetraspanin blocked EV uptake and IL-6 secretion by cholangiocytes. CONCLUSIONS:    This is the first time that EVs from a multicellular pathogen have been identified in host tissues. Our findings imply a role for O. viverrini EVs in pathogenesis and highlight an approach to vaccine development for this @entity5 .
