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

被引：78

作者：

Nieminen, Mikko T. ^{[1
,2
]}

Listyarifah, Dyah ^{[2
,3
,4
]}

Hagstrom, Jaana ^{[5
,6
,7
,8
]}

Haglund, Caj ^{[8
,9
,10
]}

Grenier, Daniel ^{[11
]}

Nordstrom, Dan ^{[12
,13
]}

Uitto, Veli-Jukka ^{[1
,2
]}

Hernandez, Marcela ^{[14
,15
,16
]}

Yucel-Lindberg, Tulay ^{[17
]}

Tervahartiala, Taina ^{[1
,2
]}

Ainola, Mari ^{[2
,4
]}

Sorsa, Timo ^{[1
,2
,17
]}

机构：

[1] Univ Helsinki, Dept Oral & Maxillofacial Dis, Haartmaninkatu 8, Helsinki 00029, Finland

[2] Univ Helsinki, Cent Hosp, Haartmaninkatu 8, Helsinki 00029, Finland

[3] Univ Gadjah Mada, Fac Dent, Dept Dent Biomed Sci, Jl Denta Sekip Utara 1, Yogyakarta 55281, Indonesia

[4] Univ Helsinki, Dept Med, Clinicum, Haartmaninkatu 8, Helsinki 00029, Finland

[5] Univ Helsinki, Haartman Inst, Dept Pathol, POB 21,Haartmaninkatu 3, FIN-00014 Helsinki, Finland

[6] Univ Helsinki, HUSLab, POB 21,Haartmaninkatu 3, FIN-00014 Helsinki, Finland

[7] Helsinki Univ Hosp, POB 21,Haartmaninkatu 3, Helsinki 00014, Finland

[8] Univ Helsinki, Translat Canc Biol, Res Program Unit, Helsinki, Finland

[9] Univ Helsinki, Dept Surg, POB 340, Helsinki 00029, Finland

[10] Univ Helsinki, Cent Hosp, POB 340, Helsinki 00029, Finland

[11] Univ Laval, Fac Med Dent, Quebec City, PQ G1V 0A6, Canada

[12] Univ Helsinki, Dept Internal Med & Rehabil, Helsinki 00029, Finland

[13] Univ Helsinki, Cent Hosp, Helsinki 00029, Finland

[14] Univ Chile, Fac Dent, Lab Periodontal Biol, Santiago, Chile

[15] Univ Chile, Fac Dent, Dept Oral Pathol & Med, Santiago, Chile

[16] Univ Autonoma Chile, Fac Hlth Sci, Dent Unit, Santiago, Chile

[17] Karolinska Inst, Dept Oral Dis, Div Periodontol, Box 4064, SE-14104 Huddinge, Sweden

来源：

BRITISH JOURNAL OF CANCER | 2018年 / 118卷 / 03期

关键词：

chymotrypsin-like proteinase; gastrointestinal cancer; oral cancer; periodontopathogen; Treponema denticola; PORPHYROMONAS-GINGIVALIS; PERIODONTAL-DISEASE; COLLAGENASE-2; MMP-8; PANCREATIC-CANCER; TISSUE INHIBITORS; HUMAN NEUTROPHIL; METALLOPROTEINASES; EXPRESSION; ALPHA-1-ANTITRYPSIN; PROGRESSION;

D O I：

10.1038/bjc.2017.409

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：428 / 434

页数：7

共 48 条

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