ArticleInternational journal for parasitology2015
Excretory/secretory products of the carcinogenic liver fluke are endocytosed by human cholangiocytes and drive cell proliferation and IL6 production.
Article in International journal for parasitology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 53 citations in OpenAlex.
- Article
- The EGFR Signaling Pathway Is Involved in the Biliary Intraepithelial Neoplasia Associated with Liver Fluke Infection.Pathogens (Basel, Switzerland) · 2025Article
- Extracellular derivatives for bone metabolism.Journal of advanced research · 2024Review
- Mechanistic insights into liver-fluke-induced bile-duct cancer.Trends in parasitology · 2024Review
- The pathogenic responses elicited during exposure of human intestinal cell line with Giardia duodenalis excretory-secretory products and the potential attributed endocytosis mechanism.Medical microbiology and immunology · 2024Article
- The crosstalk between cholangiocytes and hepatic stellate cells promotes the progression of epithelial-mesenchymal transition and periductal fibrosis during Clonorchis sinensis infection.Parasites & vectors · 2024Article
- The Parasitism and Tumors Carcinogenesis: A Review Subject.Acta parasitologica · 2024Review
- Trematode Genomics and Proteomics.Advances in experimental medicine and biology · 2024Article
- Article
- Tetraspanins from the liver fluke Opisthorchis viverrini stimulate cholangiocyte migration and inflammatory cytokine production.Folia parasitologica · 2023Article
- Tetraspanins frombioRxiv : the preprint server for biology · 2023Article
- Inflammatory Response in Caco-2 Cells Stimulated withPathogens (Basel, Switzerland) · 2022Article
- Immunolocalization and functional analysis ofParasitology · 2022Article
- Silencing ofFrontiers in cellular and infection microbiology · 2022Article
- Plasma checkpoint protein 1 (Chk1) as a potential diagnostic biomarker for opisthorchiasis and cholangiocarcinoma.Cancer biomarkers : section A of Disease markers · 2022Article
- Article
- Transcriptomic profiling of three-dimensional cholangiocyte spheroids long term exposed to repetitive Clonorchis sinensis excretory-secretory products.Parasites & vectors · 2021Article
- Review
- Intrahepatic cholangiocarcinoma: Morpho-molecular pathology, tumor reactive microenvironment, and malignant progression.Advances in cancer research · 2021Review
- Liver fluke granulin promotes extracellular vesicle-mediated crosstalk and cellular microenvironment conducive to cholangiocarcinoma.Neoplasia (New York, N.Y.) · 2020Article
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
Liver fluke infection caused by Opisthorchis viverrini remains a major public health problem in many parts of Asia including Thailand, Lao PDR, Vietnam and Cambodia, where there is a strikingly high incidence of cholangiocarcinoma (CCA - hepatic cancer of the bile duct epithelium). Among other factors, uptake of O. viverrini excretory/secretory products (OvES) by biliary epithelial cells has been postulated to be responsible for chronic inflammation and proliferation of cholangiocytes, but the mechanisms by which cells internalise O. viverrini excretory/secretory products are still unknown. Herein we incubated normal human cholangiocytes (H69), human cholangiocarcinoma cells (KKU-100, KKU-M156) and human colon cancer (Caco-2) cells with O. viverrini excretory/secretory products and analysed the effects of different endocytic inhibitors to address the mechanism of cellular uptake of ES proteins. Opisthorchis viverrini excretory/secretory products was internalised preferentially by liver cell lines, and most efficiently/rapidly by H69 cells. There was no evidence for trafficking of ES proteins to cholangiocyte organelles, and most of the fluorescence was detected in the cytoplasm. Pretreatment with clathrin inhibitors significantly reduced the uptake of O. viverrini excretory/secretory products, particularly by H69 cells. Opisthorchis viverrini excretory/secretory products induced proliferation of liver cells (H69 and CCA lines) but not intestinal (Caco-2) cells, and proliferation was blocked using inhibitors of the classical endocytic pathways (clathrin and caveolae). Opisthorchis viverrini excretory/secretory products drove IL6 secretion by H69 cells but not Caco-2 cells, and cytokine secretion was significantly reduced by endocytosis inhibitors. This the first known study to address the endocytosis of helminth ES proteins by host epithelial cells and sheds light on the pathways by which this parasite causes one of the most devastating forms of cancer in south-eastern Asia.
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