Treponema denticola chymotrypsin-like proteinase may contribute to orodigestive carcinogenesis through immunomodulation

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Nieminen , M T , Listyarifah , D , Hagström , J , Haglund , C , Grenier , D , Nordstrom , D , Uitto , V-J , Hernandez , M , Yucel-Lindberg , T , Tervahartiala , T , Ainola , M & Sorsa , T 2018 , ' Treponema denticola chymotrypsin-like proteinase may contribute to orodigestive carcinogenesis through immunomodulation ' , British Journal of Cancer , vol. 118 , no. 3 , pp. 428-434 . https://doi.org/10.1038/bjc.2017.409

Title: Treponema denticola chymotrypsin-like proteinase may contribute to orodigestive carcinogenesis through immunomodulation
Author: Nieminen, Mikko T.; Listyarifah, Dyah; Hagström, Jaana; Haglund, Caj; Grenier, Daniel; Nordstrom, Dan; Uitto, Veli-Jukka; Hernandez, Marcela; Yucel-Lindberg, Tulay; Tervahartiala, Taina; Ainola, Mari; Sorsa, Timo
Contributor: University of Helsinki, Clinicum
University of Helsinki, Clinicum
University of Helsinki, Clinicum
University of Helsinki, Translational Cancer Biology (TCB) Research Programme
University of Helsinki, Department of Medicine
University of Helsinki, Veli-Jukka Uitto / Principal Investigator
University of Helsinki, Clinicum
University of Helsinki, Clinicum
University of Helsinki, Clinicum
Date: 2018-02-07
Language: eng
Number of pages: 7
Belongs to series: British Journal of Cancer
ISSN: 0007-0920
URI: http://hdl.handle.net/10138/299680
Abstract: 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 alpha-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.
Subject: chymotrypsin-like proteinase
gastrointestinal cancer
oral cancer
periodontopathogen
Treponema denticola
PORPHYROMONAS-GINGIVALIS
PANCREATIC-CANCER
POLYMORPHONUCLEAR LEUKOCYTES
INTERSTITIAL COLLAGENASES
TUMOR MICROENVIRONMENT
PERIODONTAL-DISEASE
TISSUE INHIBITORS
HUMAN NEUTROPHIL
METALLOPROTEINASES
PROGRESSION
3122 Cancers
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