International Journal of Oral Biology

  • 제49권1호
  • /
  • Pages.1-9
  • /
  • 2024
  • /
  • 1226-7155(pISSN)
  • /
  • 2287-6618(eISSN)
대한구강생물학회 (The Korean Academy of Oral Biology)
권호 표지
DOI QR코드

DOI QR Code

Fusobacterium nucleatum infection induces CSF3 expression through p38 MAPK and JNK signaling pathways in oral squamous cell carcinoma cells

  • Ahyoung Jo (Department of Oral Biochemistry, Dental and Life Science Institute, School of Dentistry, Pusan National University) ;
  • Jung-Min Oh (Department of Oral Biochemistry, Dental and Life Science Institute, School of Dentistry, Pusan National University)
  • 투고 : 2024.01.05
  • 심사 : 2024.03.07
  • 발행 : 2024.03.31
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

Oral bacterial infections substantially affect the development of various periodontal diseases and oral cancers. However, the molecular mechanisms underlying the association between Fusobacterium nucleatum (F. nucleatum ), a major periodontitis (PT)-associated pathogen, and these diseases require extensive research. Previously, our RNA-sequencing analysis identified a few hundred differentially expressed genes in patients with PT and peri-implantitis (PI) than in healthy controls. Thus, in the present study using oral squamous cell carcinoma (OSCC) cells, we aimed to evaluate the effect of F. nucleatum infection on genes that are differentially regulated in patients with PT and PI. Human oral squamous cell carcinoma cell lines OSC-2O, HSC-4, and HN22 were used. These cells were infected with F. nucleatum at a multiplicity of infection of 100 for 3 hours at 37℃ in 5% CO2. Gene expression was then measured using reverse-transcription polymerase chain reaction. Among 18 genes tested, the expression of CSF3, an inflammation-related cytokine, was increased by F. nucleatum infection. Additionally, F. nucleatum infection increased the phosphorylation of AKT, p38 MAPK, and JNK in OSC-20 cells. Treatment with p38 MAPK (SB202190) and JNK (SP600125) inhibitors reduced the enhanced CSF3 expression induced by F. nucleatum infection. Overall, this study demonstrated that F. nucleatum promotes CSF3 expression in OSCC cells through p38 MAPK and JNK signaling pathways, suggesting that p38 MAPK and JNK inhibitors may help treat F. nucleatum-related periodontal diseases by suppressing CSF3 expression.

키워드

과제정보

This work was supported by a 2-year Research Grant of Pusan National University.

참고문헌

  1. Pihlstrom BL, Michalowicz BS, Johnson NW. Periodontal diseases. Lancet 2005;366:1809-20. doi: 10.1016/S0140-6736(05)67728-8
  2. Hajishengallis G. Periodontitis: from microbial immune subversion to systemic inflammation. Nat Rev Immunol 2015;15:30-44. doi: 10.1038/nri3785
  3. Lamont RJ, Koo H, Hajishengallis G. The oral microbiota: dynamic communities and host interactions. Nat Rev Microbiol 2018;16:745-59. doi: 10.1038/s41579-018-0089-x
  4. Bracci PM. Oral health and the oral microbiome in pancreatic cancer: an overview of epidemiological studies. Cancer J 2017;23:310-4. doi: 10.1097/PPO.0000000000000287
  5. Wang J, Yang X, Zou X, Zhang Y, Wang J, Wang Y. Relationship between periodontal disease and lung cancer: a systematic review and meta-analysis. J Periodontal Res 2020;55:581-93. doi: 10.1111/jre.12772
  6. Baima G, Ribaldone DG, Romano F, Aimetti M, Romandini M. The gum-gut axis: periodontitis and the risk of gastrointestinal cancers. Cancers (Basel) 2023;15:4594. doi: 10.3390/cancers15184594
  7. Kavarthapu A, Gurumoorthy K. Linking chronic periodontitis and oral cancer: a review. Oral Oncol 2021;121:105375. doi: 10.1016/j.oraloncology.2021.105375
  8. Cai Z, Zhu T, Liu F, Zhuang Z, Zhao L. Co-pathogens in periodontitis and inflammatory bowel disease. Front Med (Lausanne) 2021;8:723719. doi: 10.3389/fmed.2021.723719
  9. Mesa F, Mesa-Lopez MJ, Egea-Valenzuela J, Benavides-Reyes C, Nibali L, Ide M, Mainas G, Rizzo M, Magan-Fernandez A. A new comorbidity in periodontitis: Fusobacterium nucleatum and colorectal cancer. Medicina (Kaunas) 2022;58:546. doi: 10.3390/medicina58040546
  10. Liu Y, Baba Y, Ishimoto T, Iwatsuki M, Hiyoshi Y, Miyamoto Y, Yoshida N, Wu R, Baba H. Progress in characterizing the linkage between Fusobacterium nucleatum and gastrointestinal cancer. J Gastroenterol 2019;54:33-41. doi: 10.1007/s00535-018-1512-9
  11. Oh JM, Kim H. The effect of oral bacterial infection on DNA damage response in host cells. Am J Cancer Res 2023;13:3157-68.
  12. Kamarajan P, Ateia I, Shin JM, Fenno JC, Le C, Zhan L, Chang A, Darveau R, Kapila YL. Periodontal pathogens promote cancer aggressivity via TLR/MyD88 triggered activation of Integrin/FAK signaling that is therapeutically reversible by a probiotic bacteriocin. PLoS Pathog 2020;16:e1008881. doi: 10.1371/journal.ppat.1008881
  13. International Agency for Research on Cancer. Global Cancer Observatory: Cancer Today [Internet]. Lyon: International Agency for Research on Cancer [cited 2023 Dec 11]. Available from: https://gco.iarc.fr/today/onlineanalysis-table?v=2020&mode=cancer&mode_population=continents&population=900&populations=900&key=asr&sex=0&cancer=39&type=0&statistic=5&prevalence=0&population_group=0&ages_group%5B%5D=0&ages_group%5B%5D=17&group_cancer=1&include_nmsc=0&include_nmsc_other=1
  14. Warnakulasuriya S. Global epidemiology of oral and oropharyngeal cancer. Oral Oncol 2009;45:309-16. doi: 10.1016/j.oraloncology.2008.06.002
  15. Wang B, Zhang S, Yue K, Wang XD. The recurrence and survival of oral squamous cell carcinoma: a report of 275 cases. Chin J Cancer 2013;32:614-8. doi: 10.5732/cjc.012.10219
  16. Theyab A, Algahtani M, Alsharif KF, Hawsawi YM, Alghamdi A, Alghamdi A, Akinwale J. New insight into the mechanism of granulocyte colony-stimulating factor (G-CSF) that induces the mobilization of neutrophils. Hematology 2021;26:628-36. doi: 10.1080/16078454.2021.1965725
  17. Wang Y, Chen L, Liu F, Zhao N, Xu L, Fu B, Li Y. Efficacy and tolerability of granulocyte colony-stimulating factors in cancer patients after chemotherapy: a systematic review and Bayesian network meta-analysis. Sci Rep 2019;9:15374. doi: 10.1038/s41598-019-51982-4
  18. Baba M, Hasegawa H, Nakayabu M, Shimizu N, Suzuki S, Kamada N, Tani K. Establishment and characteristics of a gastric cancer cell line (HuGC-OOHIRA) producing high levels of GCSF, GM-CSF, and IL-6: the presence of autocrine growth control by G-CSF. Am J Hematol 1995;49:207-15. doi: 10.1002/ajh.2830490306
  19. Bahar B, Acedil Ayc Iota B, Coskun U, Buyukberber S, Benekli M, Yildiz R. Granulocyte colony stimulating factor (G-CSF) and macrophage colony stimulating factor (M-CSF) as potential tumor markers in non small cell lung cancer diagnosis. Asian Pac J Cancer Prev 2010;11:709-12.
  20. Matsuda A, Sasajima K, Matsutani T, Maruyama H, Miyamoto M, Yokoyama T, Suzuki S, Suzuki H, Tajiri T. Aggressive undifferentiated colon carcinoma producing granulocyte-colony stimulating factor: report of a case. Surg Today 2009;39:990-3. doi: 10.1007/s00595-008-3941-1
  21. Wang J, Yao L, Zhao S, Zhang X, Yin J, Zhang Y, Chen X, Gao M, Ling EA, Hao A, Li G. Granulocyte-colony stimulating factor promotes proliferation, migration and invasion in glioma cells. Cancer Biol Ther 2012;13:389-400. doi: 10.4161/cbt.19237
  22. Kumar J, Fraser FW, Riley C, Ahmed N, McCulloch DR, Ward AC. Granulocyte colony-stimulating factor receptor signalling via Janus kinase 2/signal transducer and activator of transcription 3 in ovarian cancer. Br J Cancer 2014;110:133-45. doi: 10.1038/bjc.2013.673. Erratum in: Br J Cancer 2015;113:1642-3.
  23. Oh JM, Kim Y, Son H, Kim YH, Kim HJ. Comparative transcriptome analysis of periodontitis and peri-implantitis in human subjects. J Periodontol 2023. doi: 10.1002/JPER.23-0289. [Epub ahead of print]
  24. Kang W, Jia Z, Tang D, Zhang Z, Gao H, He K, Feng Q. Fusobacterium nucleatum facilitates apoptosis, ROS generation, and inflammatory cytokine production by activating AKT/ MAPK and NF-κB signaling pathways in human gingival fibroblasts. Oxid Med Cell Longev 2019;2019:1681972. doi: 10.1155/2019/1681972
  25. Park SR, Kim DJ, Han SH, Kang MJ, Lee JY, Jeong YJ, Lee SJ, Kim TH, Ahn SG, Yoon JH, Park JH. Diverse Toll-like receptors mediate cytokine production by Fusobacterium nucleatum and Aggregatibacter actinomycetemcomitans in macrophages. Infect Immun 2014;82:1914-20. doi: 10.1128/IAI.01226-13
  26. Suzuki R, Kamio N, Sugimoto K, Maruoka S, Gon Y, Kaneko T, Yonehara Y, Imai K. Periodontopathic bacterium Fusobacterium nucleatum affects matrix metalloproteinase-9 expression in human alveolar epithelial cells and mouse lung. In Vivo 2022;36:649-56. doi: 10.21873/invivo.12749
  27. Saunders AS, Bender DE, Ray AL, Wu X, Morris KT. Colonystimulating factor 3 signaling in colon and rectal cancers: immune response and CMS classification in TCGA data. PLoS One 2021;16:e0247233. doi: 10.1371/journal.pone.0247233
  28. Morris KT, Khan H, Ahmad A, Weston LL, Nofchissey RA, Pinchuk IV, Beswick EJ. G-CSF and G-CSFR are highly expressed in human gastric and colon cancers and promote carcinoma cell proliferation and migration. Br J Cancer 2014;110:1211-20. doi: 10.1038/bjc.2013.822
  29. Karagiannidis I, Salataj E, Said Abu Egal E, Beswick EJ. GCSF in tumors: aggressiveness, tumor microenvironment and immune cell regulation. Cytokine 2021;142:155479. doi: 10.1016/j.cyto.2021.155479
  30. Hayashi E, Rikimaru K, Nagayama M. Simultaneous production of G- and M-CSF by an oral cancer cell line and the synergistic effects on associated leucocytosis. Eur J Cancer B Oral Oncol 1995;31B:323-7. doi: 10.1016/0964-1955(95)00038-0
  31. Fresno Vara JA, Casado E, de Castro J, Cejas P, Belda-Iniesta C, Gonzalez-Baron M. PI3K/Akt signalling pathway and cancer. Cancer Treat Rev 2004;30:193-204. doi: 10.1016/j.ctrv.2003.07.007
  32. Bubici C, Papa S. JNK signalling in cancer: in need of new, smarter therapeutic targets. Br J Pharmacol 2014;171:24-37. doi: 10.1111/bph.12432
  33. Bradham C, McClay DR. p38 MAPK in development and cancer. Cell Cycle 2006;5:824-8. doi: 10.4161/cc.5.8.2685
  34. Cuenda A, Rousseau S. p38 MAP-kinases pathway regulation, function and role in human diseases. Biochim Biophys Acta 2007;1773:1358-75. doi: 10.1016/j.bbamcr.2007.03.010
  35. Schieven GL. The biology of p38 kinase: a central role in inflammation. Curr Top Med Chem 2005;5:921-8. doi: 10.2174/1568026054985902
  36. Hammouda MB, Ford AE, Liu Y, Zhang JY. The JNK signaling pathway in inflammatory skin disorders and cancer. Cells 2020;9:857. doi: 10.3390/cells9040857
  37. Wu Q, Wu W, Jacevic V, Franca TCC, Wang X, Kuca K. Selective inhibitors for JNK signalling: a potential targeted therapy in cancer. J Enzyme Inhib Med Chem 2020;35:574-83. doi: 10.1080/14756366.2020.1720013
  38. Yong HY, Koh MS, Moon A. The p38 MAPK inhibitors for the treatment of inflammatory diseases and cancer. Expert Opin Investig Drugs 2009;18:1893-905. doi: 10.1517/13543780903321490
  39. Choi JI, Seymour GJ. Vaccines against periodontitis: a forward-looking review. J Periodontal Implant Sci 2010;40:153-63. doi: 10.5051/jpis.2010.40.4.153
  40. Kuramitsu HK, He X, Lux R, Anderson MH, Shi W. Interspecies interactions within oral microbial communities. Microbiol Mol Biol Rev 2007;71:653-70. doi: 10.1128/MMBR.00024-07
  41. Yin L, Dale BA. Activation of protective responses in oral epithelial cells by Fusobacterium nucleatum and human betadefensin-2. J Med Microbiol 2007;56(Pt 7):976-87. doi: 10.1099/jmm.0.47198-0
  42. Geng F, Zhang Y, Lu Z, Zhang S, Pan Y. Fusobacterium nucleatum caused DNA damage and promoted cell proliferation by the Ku70/p53 pathway in oral cancer cells. DNA Cell Biol 2020;39:144-51. doi: 10.1089/dna.2019.5064
  43. Zhang S, Li C, Liu J, Geng F, Shi X, Li Q, Lu Z, Pan Y. Fusobacterium nucleatum promotes epithelial-mesenchymal transiton through regulation of the lncRNA MIR4435-2HG/miR-296-5p/Akt2/SNAI1 signaling pathway. FEBS J 2020;287:4032-47. doi: 10.1111/febs.15233
  44. Udayasuryan B, Ahmad RN, Nguyen TTD, Umana A, Monet Roberts L, Sobol P, Jones SD, Munson JM, Slade DJ, Verbridge SS. Fusobacterium nucleatum induces proliferation and migration in pancreatic cancer cells through host autocrine and paracrine signaling. Sci Signal 2022;15:eabn4948. doi: 10.1126/scisignal.abn4948
  45. Michaud DS. Role of bacterial infections in pancreatic cancer. Carcinogenesis 2013;34:2193-7. doi: 10.1093/carcin/bgt249
  46. Gholizadeh P, Eslami H, Yousefi M, Asgharzadeh M, Aghazadeh M, Kafil HS. Role of oral microbiome on oral cancers, a review. Biomed Pharmacother 2016;84:552-8. doi: 10.1016/j.biopha.2016.09.082
  47. Ha NH, Park DG, Woo BH, Kim DJ, Choi JI, Park BS, Kim YD, Lee JH, Park HR. Porphyromonas gingivalis increases the invasiveness of oral cancer cells by upregulating IL-8 and MMPs. Cytokine 2016;86:64-72. doi: 10.1016/j.cyto.2016.07.013
  48. Ha NH, Woo BH, Kim DJ, Ha ES, Choi JI, Kim SJ, Park BS, Lee JH, Park HR. Prolonged and repetitive exposure to Porphyromonas gingivalis increases aggressiveness of oral cancer cells by promoting acquisition of cancer stem cell properties. Tumour Biol 2015;36:9947-60. doi: 10.1007/s13277-015-3764-9