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The GroEL protein of Porphyromonas gingivalis accelerates tumor growth by enhancing endothelial progenitor cell function and neovascularization
Authors:F‐Y. Lin  C‐Y. Huang  H‐Y. Lu  C‐M. Shih  N‐W. Tsao  S‐K. Shyue  C‐Y. Lin  Y‐J. Chang  C‐S. Tsai  Y‐W. Lin  S‐J. Lin
Affiliation:1. Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan;2. Division of Cardiology, Department of Internal Medicine and Cardiovascular Research Center, Taipei Medical University Hospital, Taipei, Taiwan;3. Division of Cardiovascular Surgery, Taipei Medical University Hospital, Taipei, Taiwan;4. Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan;5. Department of Computer Science and Information Management, Hung Kuang University, Taichung, Taiwan;6. Graduate Institute of Clinical Medicine, Taipei Medical University, Taipei, Taiwan;7. Division of Cardiovascular Surgery, National Defense Medical Center, Taipei, Taiwan;8. Institute of Oral Biology, National Yang‐Ming University, Taipei, Taiwan;9. Division of Cardiology, Taipei Veterans General Hospital, Taipei, Taiwan;10. Institute of Clinical MedicineNational Yang‐Ming University
Abstract:Porphyromonas gingivalis is a bacterial species that causes destruction of periodontal tissues. Additionally, previous evidence indicates that GroEL from P. gingivalis may possess biological activities involved in systemic inflammation, especially inflammation involved in the progression of periodontal diseases. The literature has established a relationship between periodontal disease and cancer. However, it is unclear whether P. gingivalis GroEL enhances tumor growth. Here, we investigated the effects of P. gingivalis GroEL on neovasculogenesis in C26 carcinoma cell‐carrying BALB/c mice and chick eggs in vivo as well as its effect on human endothelial progenitor cells (EPC) in vitro. We found that GroEL treatment accelerated tumor growth (tumor volume and weight) and increased the mortality rate in C26 cell‐carrying BALB/c mice. GroEL promoted neovasculogenesis in chicken embryonic allantois and increased the circulating EPC level in BALB/c mice. Furthermore, GroEL effectively stimulated EPC migration and tube formation and increased E‐selectin expression, which is mediated by eNOS production and p38 mitogen‐activated protein kinase activation. Additionally, GroEL may enhance resistance against paclitaxel‐induced cell cytotoxicity and senescence in EPC. In conclusion, P. gingivalis GroEL may act as a potent virulence factor, contributing to the neovasculogenesis of tumor cells and resulting in accelerated tumor growth.
Keywords:GroEL     Porphyromonas gingivalis     tumor
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