Tumor Biology

, Volume 36, Issue 12, pp 9947–9960 | Cite as

Prolonged and repetitive exposure to Porphyromonas gingivalis increases aggressiveness of oral cancer cells by promoting acquisition of cancer stem cell properties

  • Na Hee Ha
  • Bok Hee Woo
  • Da Jeong Kim
  • Eun Sin Ha
  • Jeom Il Choi
  • Sung Jo Kim
  • Bong Soo Park
  • Ji Hye Lee
  • Hae Ryoun ParkEmail author
Original Article


Periodontitis is the most common chronic inflammatory condition occurring in the human oral cavity, but our knowledge on its contribution to oral cancer is rather limited. To define crosstalk between chronic periodontitis and oral cancer, we investigated whether Porphyromonas gingivalis, a major pathogen of chronic periodontitis, plays a role in oral cancer progression. To mimic chronic irritation by P. gingivalis in the oral cavity, oral squamous cell carcinoma (OSCC) cells were infected with P. gingivalis twice a week for 5 weeks. Repeated infection of oral cancer cells by P. gingivalis resulted in morphological changes of host cancer cells into an elongated shape, along with the decreased expression of epithelial cell markers, suggesting acquisition of an epithelial-to-mesenchymal transition (EMT) phenotype. The prolonged exposure to P. gingivalis also promoted migratory and invasive properties of OSCC cells and provided resistance against a chemotherapeutic agent, all of which are described as cellular characteristics undergoing EMT. Importantly, long-term infection by P. gingivalis induced an increase in the expression level of CD44 and CD133, well-known cancer stem cell markers, and promoted the tumorigenic properties of infected cancer cells compared to non-infected controls. Furthermore, increased invasiveness of P. gingivalis-infected OSCC cells was correlated with enhanced production of matrix metalloproteinase (MMP)-1 and MMP-10 that was stimulated by interleukin-8 (IL-8) release. This is the first report demonstrating that P. gingivalis can increase the aggressiveness of oral cancer cells via epithelial-mesenchymal transition-like changes and the acquisition of stemness, implicating P. gingivalis as a potential bacterial risk modifier.


Porphyromonas gingivalis Oral cancer Cancer stem cell Interleukin-8 Matrix metalloproteinase Invasion 



This work was supported by Basic Science Research Program through National Research Foundation of Korea (NRF) funded by the Ministry of Education (2014R1A1A2A16050554).

Conflicts of interest



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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Na Hee Ha
    • 1
  • Bok Hee Woo
    • 1
  • Da Jeong Kim
    • 1
  • Eun Sin Ha
    • 1
  • Jeom Il Choi
    • 2
  • Sung Jo Kim
    • 2
  • Bong Soo Park
    • 3
  • Ji Hye Lee
    • 1
    • 4
  • Hae Ryoun Park
    • 1
    • 4
    Email author
  1. 1.Department of Oral Pathology, School of DentistryPusan National UniversityYangsan-SiSouth Korea
  2. 2.Department of Periodontology, School of DentistryPusan National UniversityYangsanSouth Korea
  3. 3.Department of Oral Anatomy, School of DentistryPusan National UniversityYangsanSouth Korea
  4. 4.Institute of Translational Dental SciencesPusan National UniversityYangsanSouth Korea

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