口腔および大腸発癌における微生物の役割

The Role of in Oral and Colorectal Carcinogenesis.

抄録

近年、いくつかの研究が、いくつかのヒトの癌と微生物との強い関連を示唆している。特に歯周病原性のある2つの細菌種が頻繁に言及されている。慢性歯周病は口腔扁平上皮癌（OSCC）、大腸癌（CRC）、膵臓癌の危険因子であることが報告されている。口腔プラーク形成に関与するほとんどすべての細菌種が、初期と後期のコロニー形成者の橋渡し役として働く。FadAは接着タンパク質FadAを産生し、内皮細胞ではVE-カドヘリンに、上皮細胞ではE-カドヘリンに結合する。また、Fap2タンパク質はT細胞やナチュラルキラー細胞に存在するTIGITという免疫受容体と相互作用し、免疫細胞の活動を阻害するため、免疫反応にも影響を及ぼす。さらに、外膜小胞（OMV）を放出し、炎症性サイトカインの産生を誘導し、炎症を引き起こす。口腔から遊走し、血行性に大腸に到達するが、血流中では遊離の赤血球結合菌としてCRCに到達するのか、OMVとしてCRCに到達するのかは不明である。CRC組織中の存在量は、全生存期間（OS）と逆相関している。口腔衛生の改善による歯周病の予防と治療は、がん予防プロトコルに含まれるべきである。FadAの病原性因子は、口腔癌および大腸癌の治療介入のための新規標的としても役立つ可能性がある。

In recent years, several studies have suggested a strong association of microorganisms with several human cancers. Two periodontopathogenic species in particular have been mentioned frequently: () and . Chronic periodontal disease has been reported to be a risk factor for oral squamous cell carcinoma (OSCC), colorectal cancer (CRC) and pancreatic cancer. is a Gram-negative anaerobic bacterium that lives in the oral cavity, urogenital, intestinal and upper digestive tract. It plays a significant role as a co-aggregation factor, with almost all bacterial species that participate in oral plaque formation acting as a bridge between early and late colonizers. , gives an important inflammatory contribution to tumorigenesis progression and is associated with epithelial-derived malignancies, such as OSCC and CRC. produces an adhesion protein, FadA, which binds to VE-cadherin on endothelial cells and to E-cadherins on epithelial cells. The last binding activates oncogenic pathways, such as Wnt/βcatenin, in oral and colorectal carcinogenesis. also affects immune response because its Fap2 protein interacts with an immune receptor named TIGIT present on some T cells and natural killer cells inhibiting immune cells activities. Morover, release outer membrane vesicles (OMVs), which induce the production of proinflammatory cytokines and initiating inflammation. migrates from the oral cavity and reaches the colon hematogenously but it is not known if in the bloodstream it reaches the CRC as free, erythrocyte-bound bacteria or in OMV. abundance in CRC tissue has been inversely correlated with overall survival (OS). The prevention and treatment of periodontal disease through the improvement of oral hygiene should be included in cancer prevention protocols. FadA virulence factors may also serve as novel targets for therapeutic intervention of oral and colorectal cancer.