title: Persistent Exposure toPorphyromonas gingivalisPromotes Proliferative and Invasion Capabilities, and Tumorigenic Properties of Human Immortalized Oral Epithelial Cells.
abstract: Recent epidemiological studies revealed a significant association between oral squamous cell carcinoma (OSCC) andPorphyromonas gingivalis, a major pathogen of periodontal disease. As a keystone pathogen of periodontitis,P. gingivalisis known not only to damage local periodontal tissues, but also to evade the host immune system and eventually affect systemic health. However, its role in OSCC has yet to be defined. To explore the underlying effect of chronicP. gingivalisinfection on OSCC and to identify relevant biomarkers as promising targets for therapy and prevention, we established a novel model by exposing human immortalized oral epithelial cells (HIOECs) toP. gingivalisat a low multiplicity of infection (MOI) for 5-23 weeks. TheP. gingivalisinfected HIOECs were monitored for tumor biological alteration by proliferation, wound healing, transwell invasion, and gelatin zymography assays. Microarray and proteomic analyses were performed on HIOECs infected withP. gingivalisfor 15 weeks, and some selected data were validated by quantitative real-time PCR and (or) western blot on cells infected for 15 and 23 weeks. Persistent exposure toP. gingivaliscaused cell morphological changes, increased proliferation ability with higher S phase fraction in the cell cycle, and promoted cell migratory and invasive properties. In combining results of bioinformatics analyses and validation assays, tumor-related genes such as NNMT, FLI1, GAS6, lncRNA CCAT1, PDCD1LG2, and CD274 may be considered as the key regulators in tumor-like transformation in response to long-time exposure ofP. gingivalis. In addition, some useful clinical biomarkers and novel proteins were also presented. In conclusion,P. gingivaliscould promote tumorigenic properties of HIOECs, indicating that chronicP. gingivalisinfection may be considered as a potential risk factor for oral cancer. The key regulators detected from the present model might be used in monitoring the development of OSCC with chronic periodontal infection.
authors.affiliation: Department of Periodontics, School of Stomatology, China Medical University Shenyang, China.
authors.forename: Fengxue
authors.initials: F
authors.lastname: Geng
authors.affiliation: Department of Periodontics, School of Stomatology, China Medical University Shenyang, China.
authors.forename: Junchao
authors.initials: J
authors.lastname: Liu
authors.affiliation: Key laboratory of Liaoning Province Oral Disease, School of Stomatology, China Medical UniversityShenyang, China; Department of Oral Biology, School of Stomatology, China Medical UniversityShenyang, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of Periodontics, School of Stomatology, China Medical University Shenyang, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Medicine, the Center for Immunity, Inflammation & Regenerative Medicine, University of Virginia Charlottesville, VA, USA.
authors.forename: Hongyang
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Periodontics, School of Stomatology, China Medical University Shenyang, China.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Periodontics, School of Stomatology, China Medical University Shenyang, China.
authors.forename: Haijiao
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Department of Periodontics, School of Stomatology, China Medical UniversityShenyang, China; Department of Oral Biology, School of Stomatology, China Medical UniversityShenyang, China.
authors.forename: Yaping
authors.initials: Y
authors.lastname: Pan
mesh_terms: D002460:Cell Line; D002465:Cell Movement; D049109:Cell Proliferation; D004847:Epithelial Cells / Q000382:microbiology* / Q000473:pathology*; D020869:Gene Expression Profiling; D006801:Humans; D046228:Microarray Analysis; D016966:Porphyromonas gingivalis / Q000472:pathogenicity*; D020543:Proteome / Q000032:analysis
chemical_list: D020543:Proteome
keywords: OSCC; Porphyromonas gingivalis; inflammatory microenvironment; long-term infection; tumorigenic properties