Treponema denticola chymotrypsin-like proteinase may contribute to orodigestive carcinogenesis through immunomodulation
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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 chymotrypsinlike 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 a-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.
Directorate General of Human Resource for Science, Technology and Higher Education of Indonesia, Center for International Mobility CIMO TM-15-9588 Selma and Maja-Lisa Selanders fund Otto A Malm Foundation FINDOS Sigrid Juselius Foundation Finska Lakaresallskapet FONDECYT 1160741 Helsinki University Hospital Research Foundation, Helsinki, Finland TYH 2016251 TYH 2017251 Y 1149SUL32 Karolinska Institutet, Stockholm, Sweden
Artículo de publicación ISI
Quote ItemBritish Journal of Cancer (2018) 118, 428–434
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