title: Porphyromonas gingivalis increases the invasiveness of oral cancer cells by upregulating IL-8 and MMPs.
abstract: Recent studies indicate that chronic inflammation promotes the aggressiveness of cancers. However, the direct molecular mechanisms underlying a functional link between chronic periodontitis, the most common form of oral inflammatory diseases, and the malignancy of oral cancer remain unknown. To elucidate the role of chronic periodontitis in progression of oral cancer, we examined the effect of Porphyromonas gingivalis (P. gingivalis), a major pathogen that causes chronic periodontitis, on the invasiveness of oral squamous cell carcinoma (OSCC) cells, including SCC-25, OSC-20 and SAS cells. Exposures to P. gingivalis promoted the invasive ability of OSC-20 and SAS cells via the upregulation of matrix metalloproteinases (MMPs), specifically MMP-1 and MMP-2. However, P. gingivalis-infected SCC-25 cells did not exhibit changes in their invasive properties or the low expression levels of MMPs. In an effort to delineate the molecular players that control the invasiveness, we first assessed the level of interleukin-8 (IL-8), a well-known inflammatory cytokine, in P. gingivalis-infected OSCC cells. IL-8 secretion was substantially increased in the OSC-20 and SAS cells, but not in the SCC-25 cells, following P. gingivalis infection. When IL-8 was directly applied to SCC-25 cells, their invasive ability and MMP level were significantly increased. Furthermore, the downregulation of IL-8 in P. gingivalis-infected OSC-20 and SAS cells attenuated their invasive potentials and MMP levels. Taken together, our findings strongly suggest that P. gingivalis infection plays an important role in the promotion of the invasive potential of OSCC cells via the upregulation of IL-8 and MMPs.
authors.affiliation: Department of Oral Pathology & BK21 PLUS Project, School of Dentistry, Pusan National University, 49 Busandaehak-Ro, Yangsan 50612, South Korea. Electronic address: thddlgk@gmail.com.
authors.forename: Na Hee
authors.initials: NH
authors.lastname: Ha
authors.affiliation: Department of Oral Pathology & BK21 PLUS Project, School of Dentistry, Pusan National University, 49 Busandaehak-Ro, Yangsan 50612, South Korea. Electronic address: dgnprk@gmail.com.
authors.forename: Dae Gun
authors.initials: DG
authors.lastname: Park
authors.affiliation: Department of Oral Pathology & BK21 PLUS Project, School of Dentistry, Pusan National University, 49 Busandaehak-Ro, Yangsan 50612, South Korea. Electronic address: vokiwoo@pusan.ac.kr.
authors.forename: Bok Hee
authors.initials: BH
authors.lastname: Woo
authors.affiliation: Department of Oral Pathology & BK21 PLUS Project, School of Dentistry, Pusan National University, 49 Busandaehak-Ro, Yangsan 50612, South Korea. Electronic address: ttakjjung@gmail.com.
authors.forename: Da Jeong
authors.initials: DJ
authors.lastname: Kim
authors.affiliation: Department of Periodontology, School of Dentistry, Pusan National University, 49 Busandaehak-Ro, Yangsan 50612, South Korea. Electronic address: jrapa@pusan.ac.kr.
authors.forename: Jeom Il
authors.initials: JI
authors.lastname: Choi
authors.affiliation: Department of Oral Anatomy, School of Dentistry, Pusan National University, 49 Busandaehak-Ro, Yangsan 50612, South Korea. Electronic address: parkbs@pnu.edu.
authors.forename: Bong Soo
authors.initials: BS
authors.lastname: Park
authors.affiliation: Department of Oral and Maxillofacial Surgery, School of Dentistry, Pusan National University, 49 Busandaehak-Ro, Yangsan 50612, South Korea; Institute of Translational Dental Sciences, Pusan National University, 49 Busandaehak-Ro, Yangsan 50612, South Korea. Electronic address: ydkimdds@pusan.ac.kr.
authors.forename: Yong Deok
authors.initials: YD
authors.lastname: Kim
authors.affiliation: Department of Oral Pathology & BK21 PLUS Project, School of Dentistry, Pusan National University, 49 Busandaehak-Ro, Yangsan 50612, South Korea; Institute of Translational Dental Sciences, Pusan National University, 49 Busandaehak-Ro, Yangsan 50612, South Korea. Electronic address: jihyelee@pusan.ac.kr.
authors.forename: Ji Hye
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Oral Pathology & BK21 PLUS Project, School of Dentistry, Pusan National University, 49 Busandaehak-Ro, Yangsan 50612, South Korea; Institute of Translational Dental Sciences, Pusan National University, 49 Busandaehak-Ro, Yangsan 50612, South Korea. Electronic address: parkhr@pusan.ac.kr.
authors.forename: Hae Ryoun
authors.initials: HR
authors.lastname: Park
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000382:microbiology / Q000473:pathology*; D045744:Cell Line, Tumor; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics* / Q000276:immunology; D020781:Matrix Metalloproteinase 1 / Q000235:genetics; D020778:Matrix Metalloproteinase 2 / Q000235:genetics; D020782:Matrix Metalloproteinases / Q000235:genetics*; D009062:Mouth Neoplasms / Q000378:metabolism / Q000382:microbiology / Q000473:pathology*; D009361:Neoplasm Invasiveness; D016966:Porphyromonas gingivalis / Q000502:physiology*; D060888:Real-Time Polymerase Chain Reaction; D015854:Up-Regulation
chemical_list: C508606:CXCL8 protein, human; D016209:Interleukin-8; D020782:Matrix Metalloproteinases; D020778:Matrix Metalloproteinase 2; D020781:Matrix Metalloproteinase 1
keywords: Interleukin-8; Invasion; Matrix metalloproteinase; Oral cancer; Porphyromonas gingivalis