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

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.

Comparison of inherently essential genes of Porphyromonas gingivalis identified in two transposon‐sequencing libraries

“…The heat‐shock protein 60 homologue, groEL (PGN_1452; PG0520; PGTDC_1639), is an emergent P. gingivalis virulence factor that has been proposed to promote cytokine production and inflammation, to enhance osteoclastogenesis, to aid in the vascularization of tumors and, perhaps, to play a role in atherosclerosis (Argueta et al ., ; Hagiwara et al ., ; Lin et al ., ,b). Although PGN_1452 is not itself essential, the groEL co‐chaperone, groES (PGN_1451; PG0520; PGTDC60_1640) is required for growth in complex media.…”

Prelude to oral microbes and chronic diseases: past, present and future

“…Such P. gingivalis virulence molecules and their known pathways include: distinctive fimbriae that have been shown to attenuate the host p53-mediated tumor-suppression pathways and cell-cycle progression in primary oral epithelial cells [19, 26]; cysteine proteases (gingipains) that have been suggested to be majorly involved in the activation of matrix metalloproteinases (MMPs), particularly MMP9, which are recognized to be associated with increased metastatic dissemination of carcinoma cells [19, 26]; and a nucleoside diphosphate kinase homologue (NDK), which has been demonstrated to modulate purinergic danger signaling, induce imbalance in oxidative stress metabolism, and inhibit pro-apoptotic and pro-inflammatory mechanisms in primary oral epithelial cells [32, 33]. A recent 2014 study in mice implicated another potential virulence factor from P. gingivalis – GroEL, which caused in tumor volume and weight acceleration, and in increased mortality rate of BALB/c mice implanted with a mouse-colon-carcinoma cell line (C26) [34]. GroEL is a bacterial homologue of eukaryotic heat shock protein 60 (HSP60), which is known to play a role in proper folding of mitochondrial proteins, and recently proposed to be a target for anti-cancer therapy, as well as a prognostic marker for prostate cancer [34, 35].…”

“…A recent 2014 study in mice implicated another potential virulence factor from P. gingivalis – GroEL, which caused in tumor volume and weight acceleration, and in increased mortality rate of BALB/c mice implanted with a mouse-colon-carcinoma cell line (C26) [34]. GroEL is a bacterial homologue of eukaryotic heat shock protein 60 (HSP60), which is known to play a role in proper folding of mitochondrial proteins, and recently proposed to be a target for anti-cancer therapy, as well as a prognostic marker for prostate cancer [34, 35]. This study examined the effect of GroEL using a recombinant protein approach and mice carrying an already established tumor cell line (C26).…”

Identification of Bacteria Involved in Periodontal Disease Using Molecular Biology Techniques

“…To a certain extent, the chronic and aggressive periodontitis, share many clinical features, but the specific details of their common characteristics are not necessarily identical in both forms of the disease [6]. Thus far, it was determined that both are complex infections that occur in susceptible hosts caused by biofilms that form on the surfaces of the teeth [7,8]. The ability to form biofilms, considered recently the attribute only for a few species is now seen as an attribute for almost all microorganisms [9,10].…”