Treponema denticola chymotrypsin-like proteinase may contribute to orodigestive carcinogenesis through immunomodulation
Autor
Nieminen M.T.
Listyarifah D.
Hagström J.
Haglund C.
Grenier D.
Nordström D.
Uitto V.-J.
Hernandez M.
Yucel-Lindberg T.
Tervahartiala T.
Ainola M.
Sorsa T.
Resumen
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.
Colecciones
Ítems relacionados
Mostrando ítems relacionados por Título, autor o materia.
-
Review
Osteoimmunology of oral and maxillofacial diseases: Translational applications based on biological mechanisms (2020)
Alvarez C.; Monasterio G.; Cavalla F.; Córdova L.A.; Hernández M.; Heymann D.; Garlet G.P.; Sorsa T.; Pärnänen P.; Lee H.-M.; ... (Frontiers Media S.A., 2019) -
Article
Treponema denticola chymotrypsin-like proteinase is present in early-stage mobile tongue squamous cell carcinoma and related to the clinicopathological features (2020)
Listyarifah D.; Nieminen M.T.; Mäkinen L.K.; Haglund C.; Grenier D.; Häyry V.; Nordström D.; Hernandez M.; Yucel-Lindberg T.; Tervahartiala T.; ... (Blackwell Publishing Ltd, 2018) -
Article
Cleavage of Fibulin-2 by the aggrecanases ADAMTS-4 and ADAMTS-5 contributes to the tumorigenic potential of breast cancer cells (2020)
Fontanil T.; álvarez-Teijeiro S.; Villaronga M.Á.; Mohamedi Y.; Solares L.; Moncada-Pazos A.; Vega J.A.; García-Suárez O.; Pérez-Basterrechea M.; García-Pedrero J.M.; ... (Impact Journals LLC, 2017)