Periodontal pathogens Porphyromonas gingivalis and Fusobacterium nucleatum promote tumor progression in an oral-specific chemical carcinogenesis model.
Periodontal pathogens Porphyromonas gingivalis and Fusobacterium nucleatum promote tumor progression in an oral-specific chemical carcinogenesis model.
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DOI：
10.18632/oncotarget.4209
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发表时间：
2015-09-08
期刊：
影响因子：
--
通讯作者：
Elkin M
中科院分区：
文献类型：
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作者：
Binder Gallimidi A;Fischman S;Revach B;Bulvik R;Maliutina A;Rubinstein AM;Nussbaum G;Elkin M
口腔鳞状细胞癌（OSCC）是一种致命疾病，其发病率正在上升。流行病学研究表明牙周炎与口腔癌之间存在关联，并且牙周病原体与许多疾病的发病机制有关，包括类风湿性关节炎、心血管疾病、糖尿病和胃肠道恶性肿瘤。然而，牙周病原体在口腔鳞状细胞癌中的致病作用尚未得到证实，部分原因是缺乏合适的动物模型。在此，利用一种新建立的牙周炎相关口腔肿瘤发生的小鼠模型，我们报告慢性细菌感染促进口腔鳞状细胞癌，并且沿白细胞介素 - 6 - 信号转导及转录激活因子3（IL - 6 - STAT3）轴的信号增强是这种效应的基础。我们的结果表明，牙周病原体牙龈卟啉单胞菌和具核梭杆菌通过Toll样受体与口腔上皮细胞直接相互作用刺激肿瘤发生。此外，口腔病原体刺激人类口腔鳞状细胞癌增殖并诱导与肿瘤发生有关的关键分子的表达。据我们所知，这些发现首次证明了口腔细菌在化学诱导的口腔鳞状细胞癌肿瘤发生中的机制作用。这些结果对设计有效的口腔鳞状细胞癌预防和治疗策略具有高度相关性。
Oral squamous cell carcinoma (OSCC) is a lethal disease whose incidence is increasing. Epidemiologic studies demonstrate an association between periodontitis and oral cancer, and periodontal pathogens are implicated in the pathogenesis of numerous disorders, including rheumatoid arthritis, cardiovascular diseases, diabetes and gastrointestinal malignancies. Nevertheless, a causal role for periodontal pathogens in OSCC has not been shown, partly due to the lack of an appropriate animal model. Here, utilizing a newly-established murine model of periodontitis-associated oral tumorigenesis, we report that chronic bacterial infection promotes OSCC, and that augmented signaling along the IL-6-STAT3 axis underlies this effect. Our results indicate that periodontal pathogens P. gingivalis and F. nucleatum stimulate tumorigenesis via direct interaction with oral epithelial cells through Toll-like receptors. Furthermore, oral pathogens stimulate human OSCC proliferation and induce expression of key molecules implicated in tumorigenesis. To the best of our knowledge, these findings represent the first demonstration of a mechanistic role for oral bacteria in chemically induced OSCC tumorigenesis. These results are highly relevant for the design of effective prevention and treatment strategies for OSCC.