The GroEL protein of Porphyromonas gingivalis accelerates tumor growth by enhancing endothelial progenitor cell function and neovascularization

• Published in: Molecular oral microbiology Vol. 30; no. 3; pp. 198 - 216
• Main Authors: Lin, F-Y., Huang, C-Y., Lu, H-Y., Shih, C-M., Tsao, N-W., Shyue, S-K., Lin, C-Y., Chang, Y-J., Tsai, C-S., Lin, Y-W., Lin, S-J.
• Format: Journal Article
• Language: English
• Published: Denmark Blackwell Publishing Ltd 01.06.2015
• Subjects: Allantois - blood supply; Animals; Bacterial Proteins - metabolism; Cell Line, Tumor; Chaperonin 60 - metabolism; Chick Embryo; Colonic Neoplasms - microbiology; Dentistry; E-Selectin - metabolism; Endothelial Progenitor Cells - cytology; Endothelial Progenitor Cells - metabolism; GroEL; Humans; Male; Mice; Mice, Inbred BALB C; Microscopy, Confocal; Neovascularization, Physiologic; Nitric Oxide Synthase Type III - metabolism; p38 Mitogen-Activated Protein Kinases - metabolism; Phosphorylation; Porphyromonas gingivalis; Porphyromonas gingivalis - genetics; Porphyromonas gingivalis - pathogenicity; Recombinant Proteins - metabolism; tumor; Virulence Factors - metabolism; Porphyromonas gingivalis; GroEL; tumor
• ISSN: 2041-1006; 2041-1014
• DOI: 10.1111/omi.12083

Summary 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.