The oral bacterium Streptococcus mutans promotes tumor metastasis by inducing vascular inflammation

Abstract

Recent studies have demonstrated a relationship between oral bacteria and systemic inflammation. Endothelial cells (ECs), which line blood vessels, control the opening and closing of the vascular barrier and contribute to hematogenous metastasis; however, the role of oral bacteria‐induced vascular inflammation in tumor metastasis remains unclear. In this study, we examined the phenotypic changes in vascular ECs following Streptococcus mutans (S. mutans) stimulation in vitro and in vivo. The expression of molecules associated with vascular inflammation and barrier‐associated adhesion was analyzed. Tumor metastasis was evaluated after intravenous injection of S. mutans in murine breast cancer hematogenous metastasis model. The results indicated that S. mutans invaded the ECs accompanied by inflammation and NF‐κB activation. S. mutans exposure potentially disrupts endothelial integrity by decreasing vascular endothelial (VE)‐cadherin expression. The migration and adhesion of tumor cells were enhanced in S. mutans‐stimulated ECs. Furthermore, S. mutans‐induced lung vascular inflammation promoted breast cancer cell metastasis to the lungs in vivo. The results indicate that oral bacteria promote tumor metastasis through vascular inflammation and the disruption of vascular barrier function. Improving oral hygiene in patients with cancer is of great significance in preventing postoperative pneumonia and tumor metastasis.

Reverse effects of Streptococcus mutans physiological states on neutrophil extracellular traps formation as a strategy to escape neutrophil killing

“…Interestingly, our histological findings were inconsistent with the results of others in that whether S. mutans could induce significant histopathological changes or not in vivo animal study. For example, by infection with S. mutans, Velusamy et al demonstrated the infiltrated with inflammatory cells and abnormal structures of the lung alveoli with thickening alveolar walls in lung tissues; prominent accumulation of lipids and macrovesicular appearance along with ballooning and vacuolization of hepatocytes and significant infiltration of inflammatory cells in liver, and splenomegaly and infiltrations of increasing inflammatory cells in spleen specimen (Kim et al, 2012;Hong et al, 2014;Naka et al, 2014;Velusamy et al, 2014;Naka et al, 2016;Yu et al, 2022). However, the duration of bacterial infection was much longer in those studies, and this helped to explain the inconsistent results partly.…”

Oral bacterium Streptococcus mutans promotes tumor metastasis through thrombosis formation

“…Total RNA was isolated from nonstimulated and S. mutans ‐stimulated MS1 cells using the Relia‐Prep RNA Miniprep System, followed by quality identification using an RNA 6000 Nano Assay Kit and a 2100 Bioanalyzer (Agilent Technologies). Subsequently, next‐generation sequencing for RNA‐seq was carried out by Takara Bio Inc. as previously reported 1 . Pathway analysis was undertaken using IPA software (Qiagen).…”

“…Mouse lung inflammation and lung tumor metastasis models with or without aspirin therapy were created using 6‐week‐old female C57BL/6 mice purchased from CLEA Japan as previously reported 1 . The lung inflammation model was created by intravenous implantation of 1 × 10 5 CFUs of S. mutans suspensions into the mouse tail vein every 2 days for a total of eight injections (PBS implantation as a control), and the mice were killed 1 day after the final implantation.…”

“…We 3A). 1 Hematoxylin-eosin staining was used to evaluate lung inflammation, which demonstrated accumulation of inflammatory cells in the lung tissues of mice implanted with S. mutans (Figure 3B). CD41 is a platelet surface marker, 23 and P-selectin is an established platelet activation marker.…”

“…Thrombosis is induced by vascular inflammation, followed by secretion of procoagulation factors from inflamed ECs, such as vWF, to recruit platelets and form thrombosis 16,17 . Our previous study has reported that S. mutans induces vascular inflammation by invading the ECs and that S. mutans stimulation promotes tumor metastasis 1 . However, the molecular basis of whether S. mutans ‐mediated vascular inflammation induces thrombosis and further contributes to thrombosis‐facilitated tumor metastasis remains unclear.…”