ArticleNeoplasia (New York, N.Y.)2020
Liver fluke granulin promotes extracellular vesicle-mediated crosstalk and cellular microenvironment conducive to cholangiocarcinoma.
Article in Neoplasia (New York, N.Y.), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 24 citations in OpenAlex.
- Macrophage-Derived Extracellular Vesicles Deliver Progranulin to Alleviate Skin Wound Fibrosis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- A Hidden "Promoter":Infection and immunity · 2026Article
- Human Alveolar Echinococcosis-A Neglected Zoonotic Disease Requiring Urgent Attention.International journal of molecular sciences · 2025Review
- Liver Fluke-Derived Molecules Accelerate Skin Repair Processes in a Mouse Model of Type 2 Diabetes Mellitus.International journal of molecular sciences · 2024Article
- Getting off tract: contributions of intraorgan microbiota to cancer in extraintestinal organs.Gut · 2023Review
- The Arising Role of Extracellular Vesicles in Cholangiocarcinoma: A Rundown of the Current Knowledge Regarding Diagnostic and Therapeutic Approaches.International journal of molecular sciences · 2023Review
- Extracellular Vesicles in Hepatobiliary Health and Disease.Comprehensive Physiology · 2023Review
- Infectious Agents Induce Wnt/β-Catenin Pathway Deregulation in Primary Liver Cancers.Microorganisms · 2023Review
- Review
- Similarities and differences among the Opisthorchiidae liver flukes: insights fromParasitology · 2022Review
- LIN28B Enhanced STAT3 Signaling Regulates Inflammatory Response and Chemotherapeutic Resistance in Cholangiocytes.Asian Pacific journal of cancer prevention : APJCP · 2021Article
- Review
- Review
- Article
- Integrative Transcriptomics and Proteomics Analyses to Reveal the Developmental Regulation ofFrontiers in cellular and infection microbiology · 2021Article
- Infection withPathogens (Basel, Switzerland) · 2020Article
Corrections and comments
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Authors and funding
14 authors at 6 institutions in 4 countries.
Funding
Abstract
Crosstalk between malignant and neighboring cells contributes to tumor growth. In East Asia, infection with the liver fluke is a major risk factor for cholangiocarcinoma (CCA). The liver fluke Opisthorchis viverrini secretes a growth factor termed liver fluke granulin, a homologue of the human progranulin, which contributes significantly to biliary tract fibrosis and morbidity. Here, extracellular vesicle (EV)-mediated transfer of mRNAs from human cholangiocytes to naïve recipient cells was investigated following exposure to liver fluke granulin. To minimize the influence of endogenous progranulin, its cognate gene was inactivated using CRISPR/Cas9-based gene knock-out. Several progranulin-depleted cell lines, termed ΔhuPGRN-H69, were established. These lines exhibited >80% reductions in levels of specific transcript and progranulin, both in gene-edited cells and within EVs released by these cells. Profiles of extracellular vesicle RNAs (evRNA) from ΔhuPGRN-H69 for CCA-associated characteristics revealed a paucity of transcripts for estrogen- and Wnt-signaling pathways, peptidase inhibitors and tyrosine phosphatase related to cellular processes including oncogenic transformation. Several CCA-specific evRNAs including MAPK/AKT pathway members were induced by exposure to liver fluke granulin. By comparison, estrogen, Wnt/PI3K and TGF signaling and other CCA pathway mRNAs were upregulated in wild type H69 cells exposed to liver fluke granulin. Of these, CCA-associated evRNAs modified the CCA microenvironment in naïve cells co-cultured with EVs from ΔhuPGRN-H69 cells exposed to liver fluke granulin, and induced translation of MAPK phosphorylation related-protein in naïve recipient cells in comparison with control recipient cells. Exosome-mediated crosstalk in response to liver fluke granulin promoted a CCA-specific program through MAPK pathway which, in turn, established a CCA-conducive disposition.
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Registered trials
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