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Treponema denticola chymotrypsin-like proteinase may contribute to orodigestive carcinogenesis through immunomodulation
BACKGROUND: Periodontal pathogens have been linked to oral and gastrointestinal (orodigestive) carcinogenesis. However, the exact mechanisms remain unknown. Treponema denticola (Td) is associated with severe periodontitis, a chronic inflammatory disease leading to tooth loss. The anaerobic spirochet...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5808028/ https://www.ncbi.nlm.nih.gov/pubmed/29149107 http://dx.doi.org/10.1038/bjc.2017.409 |
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author | Nieminen, Mikko T Listyarifah, Dyah Hagström, Jaana Haglund, Caj Grenier, Daniel Nordström, Dan Uitto, Veli-Jukka Hernandez, Marcela Yucel-Lindberg, Tülay Tervahartiala, Taina Ainola, Mari Sorsa, Timo |
author_facet | Nieminen, Mikko T Listyarifah, Dyah Hagström, Jaana Haglund, Caj Grenier, Daniel Nordström, Dan Uitto, Veli-Jukka Hernandez, Marcela Yucel-Lindberg, Tülay Tervahartiala, Taina Ainola, Mari Sorsa, Timo |
author_sort | Nieminen, Mikko T |
collection | PubMed |
description | BACKGROUND: Periodontal pathogens have been linked to oral and gastrointestinal (orodigestive) carcinogenesis. However, the exact mechanisms remain unknown. Treponema denticola (Td) is associated with severe periodontitis, a chronic inflammatory disease leading to tooth loss. The anaerobic spirochete Td is an invasive bacteria due to its major virulence factor chymotrypsin-like proteinase. Here we aimed to investigate the presence of Td chymotrypsin-like proteinase (Td-CTLP) in major orodigestive tumours and to elucidate potential mechanisms for Td to contribute to carcinogenesis. METHODS: The presence of Td-CTLP within orodigestive tumour tissues was examined using immunohistochemistry. Oral, tonsillar, and oesophageal squamous cell carcinomas, alongside gastric, pancreatic, and colon adenocarcinomas were stained with a Td-CTLP-specific antibody. Gingival tissue from periodontitis patients served as positive controls. SDS–PAGE and immunoblot were used to analyse the immumodulatory activity of Td-CTLP in vitro. RESULTS: Td-CTLP was present in majority of orodigestive tumour samples. Td-CTLP was found to convert pro MMP-8 and -9 into their active forms. In addition, Td-CTLP was able to degrade the proteinase inhibitors TIMP-1, TIMP-2, and α-1-antichymotrypsin, as well as complement C1q. CONCLUSIONS: Because of its presence within tumours and regulatory activity on proteins critical for the regulation of tumour microenvironment and inflammation, the Td-CTLP may contribute to orodigestive carcinogenesis. |
format | Online Article Text |
id | pubmed-5808028 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-58080282019-02-06 Treponema denticola chymotrypsin-like proteinase may contribute to orodigestive carcinogenesis through immunomodulation Nieminen, Mikko T Listyarifah, Dyah Hagström, Jaana Haglund, Caj Grenier, Daniel Nordström, Dan Uitto, Veli-Jukka Hernandez, Marcela Yucel-Lindberg, Tülay Tervahartiala, Taina Ainola, Mari Sorsa, Timo Br J Cancer Molecular Diagnostics BACKGROUND: Periodontal pathogens have been linked to oral and gastrointestinal (orodigestive) carcinogenesis. However, the exact mechanisms remain unknown. Treponema denticola (Td) is associated with severe periodontitis, a chronic inflammatory disease leading to tooth loss. The anaerobic spirochete Td is an invasive bacteria due to its major virulence factor chymotrypsin-like proteinase. Here we aimed to investigate the presence of Td chymotrypsin-like proteinase (Td-CTLP) in major orodigestive tumours and to elucidate potential mechanisms for Td to contribute to carcinogenesis. METHODS: The presence of Td-CTLP within orodigestive tumour tissues was examined using immunohistochemistry. Oral, tonsillar, and oesophageal squamous cell carcinomas, alongside gastric, pancreatic, and colon adenocarcinomas were stained with a Td-CTLP-specific antibody. Gingival tissue from periodontitis patients served as positive controls. SDS–PAGE and immunoblot were used to analyse the immumodulatory activity of Td-CTLP in vitro. RESULTS: Td-CTLP was present in majority of orodigestive tumour samples. Td-CTLP was found to convert pro MMP-8 and -9 into their active forms. In addition, Td-CTLP was able to degrade the proteinase inhibitors TIMP-1, TIMP-2, and α-1-antichymotrypsin, as well as complement C1q. CONCLUSIONS: Because of its presence within tumours and regulatory activity on proteins critical for the regulation of tumour microenvironment and inflammation, the Td-CTLP may contribute to orodigestive carcinogenesis. Nature Publishing Group 2018-02-06 2017-11-16 /pmc/articles/PMC5808028/ /pubmed/29149107 http://dx.doi.org/10.1038/bjc.2017.409 Text en Copyright © 2018 Cancer Research UK http://creativecommons.org/licenses/by-nc-sa/4.0/ From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 4.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/4.0/ |
spellingShingle | Molecular Diagnostics Nieminen, Mikko T Listyarifah, Dyah Hagström, Jaana Haglund, Caj Grenier, Daniel Nordström, Dan Uitto, Veli-Jukka Hernandez, Marcela Yucel-Lindberg, Tülay Tervahartiala, Taina Ainola, Mari Sorsa, Timo Treponema denticola chymotrypsin-like proteinase may contribute to orodigestive carcinogenesis through immunomodulation |
title | Treponema denticola chymotrypsin-like proteinase may contribute to orodigestive carcinogenesis through immunomodulation |
title_full | Treponema denticola chymotrypsin-like proteinase may contribute to orodigestive carcinogenesis through immunomodulation |
title_fullStr | Treponema denticola chymotrypsin-like proteinase may contribute to orodigestive carcinogenesis through immunomodulation |
title_full_unstemmed | Treponema denticola chymotrypsin-like proteinase may contribute to orodigestive carcinogenesis through immunomodulation |
title_short | Treponema denticola chymotrypsin-like proteinase may contribute to orodigestive carcinogenesis through immunomodulation |
title_sort | treponema denticola chymotrypsin-like proteinase may contribute to orodigestive carcinogenesis through immunomodulation |
topic | Molecular Diagnostics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5808028/ https://www.ncbi.nlm.nih.gov/pubmed/29149107 http://dx.doi.org/10.1038/bjc.2017.409 |
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