2015
DOI: 10.1093/infdis/jiv291
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Carcinogenic Liver Fluke Secretes Extracellular Vesicles That Promote Cholangiocytes to Adopt a Tumorigenic Phenotype

Abstract: Background. Throughout Asia, there is an unprecedented link between cholangiocarcinoma and infection with the liver fluke Opisthorchis viverrini. Multiple processes, including chronic inflammation and secretion of parasite proteins into the biliary epithelium, drive infection toward cancer. 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… Show more

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Cited by 141 publications
(141 citation statements)
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“…Excretory-secretory products of O. viverrini induce expression of Interleukin-6 (IL-6) (50) . Extracellular vesicles containing excretorysecretory products, are taken up by cholangiocytes, and induce release of IL-6, as well as changes in protein expression associated with cancer (51) . IL-6 drives release of human pro-granulin, which is associated with development of many cancers, including cholangiocarcinoma (52) , and may represent a biomarker for development of advanced periportal fibrosis and cholangiocarcinoma (36,50) .…”
Section: Cholangiocarcinomamentioning
confidence: 99%
“…Excretory-secretory products of O. viverrini induce expression of Interleukin-6 (IL-6) (50) . Extracellular vesicles containing excretorysecretory products, are taken up by cholangiocytes, and induce release of IL-6, as well as changes in protein expression associated with cancer (51) . IL-6 drives release of human pro-granulin, which is associated with development of many cancers, including cholangiocarcinoma (52) , and may represent a biomarker for development of advanced periportal fibrosis and cholangiocarcinoma (36,50) .…”
Section: Cholangiocarcinomamentioning
confidence: 99%
“…Helminth EVs have immunomodulatory effects and contribute to pathogenesis. For instance, EVs secreted by parasitic flatworms can promote tumorigenesis [18] and polarize host macrophages towards a M1 phenotype [19], while EVs from the gastrointestinal nematode Heligmosomoides polygyrus contain small RNAs that can modulate host innate immunity [20]. …”
Section: Introductionmentioning
confidence: 99%
“…It is believed that liver flukes can cause damage to the bile duct epithelium in several ways: (i) via mechanical damage; (ii) as a result of action of reactive oxygen species that are produced by the host cells at the site of inflammation; and (iii) because of direct action of fluke-secreted proteins that induce cell proliferation and inhibit apoptosis [3436]. All these processes lead to lesions in the genetic material and mutations, which get fixed after DNA replication.…”
Section: Discussionmentioning
confidence: 99%