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Tetraspanins from Opisthorchis viverrini stimulate cholangiocyte migration and inflammatory cytokine production
The liver fluke Opsithorchis viverrini secretes extracellular vesicles (EVs) bearing CD63-like tetraspanins on their surface. Fluke EVs are actively internalized by host cholangiocytes in the bile ducts, where they drive pathology and promote neoplasia through induction of cellular proliferation and...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Cold Spring Harbor Laboratory
2023
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10312640/ https://www.ncbi.nlm.nih.gov/pubmed/37398394 http://dx.doi.org/10.1101/2023.06.12.544604 |
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author | Ruangsuwast, Apisit Smout, Michael J. Brindley, Paul J. Loukas, Alex Laha, Thewarach Chaiyadet, Sujittra |
author_facet | Ruangsuwast, Apisit Smout, Michael J. Brindley, Paul J. Loukas, Alex Laha, Thewarach Chaiyadet, Sujittra |
author_sort | Ruangsuwast, Apisit |
collection | PubMed |
description | The liver fluke Opsithorchis viverrini secretes extracellular vesicles (EVs) bearing CD63-like tetraspanins on their surface. Fluke EVs are actively internalized by host cholangiocytes in the bile ducts, where they drive pathology and promote neoplasia through induction of cellular proliferation and secretion of inflammatory cytokines. We investigated the effects of tetraspanins of the CD63 superfamily by co-culturing recombinant forms of the large extracellular loop (LEL) of O. viverrini tetraspanin-2 (rLEL-Ov-TSP-2) and tetraspanin-3 (rLEL-Ov-TSP-3) with non-cancerous human bile duct (H69) and cholangiocarcinoma (CCA, M213) cell lines. The results showed that cell lines co-cultured with excretory/secretory products from adult O. viverrini (Ov-ES) underwent significantly increased cell proliferation at 48 hours but not 24 hours compared to untreated control cells (P<0.05), whereas rLEL-Ov-TSP-3 co-culture resulted in significantly increased cell proliferation at both 24 hr (P<0.05) and 48 hr (P<0.01) time points. In like fashion, H69 cholangiocytes co-cultured with both Ov-ES and rLEL-Ov-TSP-3 underwent significantly elevated Il-6 and Il-8 gene expression for at least one of the time points assessed. Finally, both rLEL-Ov-TSP- and rLEL-Ov-TSP-3 significantly enhanced migration of both M213 and H69 cell lines. These findings indicated that O. viverrini CD63 family tetraspanins can promote a cancerous microenvironment by enhancing innate immune responses and migration of biliary epithelial cells. |
format | Online Article Text |
id | pubmed-10312640 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Cold Spring Harbor Laboratory |
record_format | MEDLINE/PubMed |
spelling | pubmed-103126402023-07-01 Tetraspanins from Opisthorchis viverrini stimulate cholangiocyte migration and inflammatory cytokine production Ruangsuwast, Apisit Smout, Michael J. Brindley, Paul J. Loukas, Alex Laha, Thewarach Chaiyadet, Sujittra bioRxiv Article The liver fluke Opsithorchis viverrini secretes extracellular vesicles (EVs) bearing CD63-like tetraspanins on their surface. Fluke EVs are actively internalized by host cholangiocytes in the bile ducts, where they drive pathology and promote neoplasia through induction of cellular proliferation and secretion of inflammatory cytokines. We investigated the effects of tetraspanins of the CD63 superfamily by co-culturing recombinant forms of the large extracellular loop (LEL) of O. viverrini tetraspanin-2 (rLEL-Ov-TSP-2) and tetraspanin-3 (rLEL-Ov-TSP-3) with non-cancerous human bile duct (H69) and cholangiocarcinoma (CCA, M213) cell lines. The results showed that cell lines co-cultured with excretory/secretory products from adult O. viverrini (Ov-ES) underwent significantly increased cell proliferation at 48 hours but not 24 hours compared to untreated control cells (P<0.05), whereas rLEL-Ov-TSP-3 co-culture resulted in significantly increased cell proliferation at both 24 hr (P<0.05) and 48 hr (P<0.01) time points. In like fashion, H69 cholangiocytes co-cultured with both Ov-ES and rLEL-Ov-TSP-3 underwent significantly elevated Il-6 and Il-8 gene expression for at least one of the time points assessed. Finally, both rLEL-Ov-TSP- and rLEL-Ov-TSP-3 significantly enhanced migration of both M213 and H69 cell lines. These findings indicated that O. viverrini CD63 family tetraspanins can promote a cancerous microenvironment by enhancing innate immune responses and migration of biliary epithelial cells. Cold Spring Harbor Laboratory 2023-06-12 /pmc/articles/PMC10312640/ /pubmed/37398394 http://dx.doi.org/10.1101/2023.06.12.544604 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator. |
spellingShingle | Article Ruangsuwast, Apisit Smout, Michael J. Brindley, Paul J. Loukas, Alex Laha, Thewarach Chaiyadet, Sujittra Tetraspanins from Opisthorchis viverrini stimulate cholangiocyte migration and inflammatory cytokine production |
title | Tetraspanins from Opisthorchis viverrini stimulate cholangiocyte migration and inflammatory cytokine production |
title_full | Tetraspanins from Opisthorchis viverrini stimulate cholangiocyte migration and inflammatory cytokine production |
title_fullStr | Tetraspanins from Opisthorchis viverrini stimulate cholangiocyte migration and inflammatory cytokine production |
title_full_unstemmed | Tetraspanins from Opisthorchis viverrini stimulate cholangiocyte migration and inflammatory cytokine production |
title_short | Tetraspanins from Opisthorchis viverrini stimulate cholangiocyte migration and inflammatory cytokine production |
title_sort | tetraspanins from opisthorchis viverrini stimulate cholangiocyte migration and inflammatory cytokine production |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10312640/ https://www.ncbi.nlm.nih.gov/pubmed/37398394 http://dx.doi.org/10.1101/2023.06.12.544604 |
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