The basic study of oral squamous cell carcinoma metastasis related with periodontal pathogen

2016 Fiscal Year Final Research Report

• Project/Area Number: 25462850
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Morphological basic dentistry
• Research Institution: Okayama University (2015-2016); Asahi University (2014); Osaka University (2013)
• Principal Investigator: Inaba Hiroaki 岡山大学, 医歯薬学総合研究科, 准教授 (70359850)
• Research Collaborator: Lamont Richard J
• Project Period (FY): 2013-04-01 – 2017-03-31
• Keywords: P. gingivalis / タンパク分解酵素 / 歯周病 / 口腔癌 / 浸潤・転移 / シグナル伝達 / マトリックスメタロプロテアーゼ

Outline of Final Research Achievements

Matrix metalloproteinase 9 (MMP9) is implicated in the invasion and metastasis　of tumor cells. We examined the involvement of Porphyromonas gingivalis, a periodontal pathogen, in oral squamous cell carcinoma (OSCC) cell lines invasion through induced proMMP9 production and its activation. P. gingivalis also stimulated proteinase-activated receptor 2 (PAR2) and 4, and enhanced proMMP9 expression, which promoted cellular invasion. Infected OSCC cells exhibited activation of ERK1/2, p38, and NF-kB, and their inhibitors diminished both proMMP9 production and cellular invasion. Together, our results show that P. gingivalis activated the PAR2/NF-kB, PAR4-ERK1/2-Ets1 and PAR4/p38/HSP27 pathways to induce proMMP9 expression, after which the proenzyme was activated by proteases to promote cellular invasion of OSCC cell lines. In addition, our data show that apple- and hop-polyphenols were potent inhibitors of proMMP9 activation and cellular invasion mediated with P. gingivalis.

Free Research Field

医歯薬学　歯学　形態系基礎歯科学　口腔細菌学