Artículos de revistas
Treponema denticola chymotrypsin-like proteinase may contribute to orodigestive carcinogenesis through immunomodulation
Fecha
2018Registro en:
British Journal of Cancer (2018) 118, 428–434
10.1038/bjc.2017.409
Autor
Nieminen, Mikko T.
Listyarifah, Dyah
Hagstrom, Jaana
Haglund, Caj
Grenier, Daniel
Nordstrom, Dan
Uitto, Veli-Jukka
Hernández Ríos, Emma
Yucel-Lindberg, Tulay
Tervahartiala, Taina
Ainola, Mari
Sorsa, Timo
Institución
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 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.