Vascular Biology and Molecular Pathology, Faculty of Dental Medicine and Graduate School of Dental Medicine, Hokkaido University, Sapporo, Japan.
Oral Diagnosis and Medicine, Faculty of Dental Medicine and Graduate School of Dental Medicine, Hokkaido University, Sapporo, Japan.
Cancer Sci. 2024 Feb;115(2):648-659. doi: 10.1111/cas.16010. Epub 2023 Dec 14.
Thrombosis is a well-known cardiovascular disease (CVD) complication that has caused death in many patients with cancer. Oral bacteria have been reported to contribute to systemic diseases, including CVDs, and tumor metastasis. However, whether oral bacteria-induced thrombosis induces tumor metastasis remains poorly understood. In this study, the cariogenic oral bacterium Streptococcus mutans was used to examine thrombosis in vitro and in vivo. Investigation of tumor metastasis to the lungs was undertaken by intravenous S. mutans implantation using a murine breast cancer metastasis model. The results indicated that platelet activation, aggregation, and coagulation were significantly altered in S. mutans-stimulated endothelial cells (ECs), with elevated neutrophil migration, thereby inducing thrombosis formation. Streptococcus mutans stimulation significantly enhances platelet and tumor cell adhesion to the inflamed ECs. Furthermore, S. mutans-induced pulmonary thrombosis promotes breast cancer cell metastasis to the lungs in vivo, which can be reduced by using aspirin, an antiplatelet drug. Our findings indicate that oral bacteria promote tumor metastasis through thrombosis formation. Oral health management is important to prevent CVDs, tumor metastasis, and their associated death.
血栓形成是一种众所周知的心血管疾病（CVD）并发症，已导致许多癌症患者死亡。据报道，口腔细菌会导致全身性疾病，包括 CVD 和肿瘤转移。然而，口腔细菌诱导的血栓形成是否会引起肿瘤转移尚不清楚。在这项研究中，使用致龋口腔细菌变形链球菌来研究体外和体内的血栓形成。通过使用小鼠乳腺癌转移模型静脉内植入 S. mutans 来研究肿瘤转移到肺部的情况。结果表明，在 S. mutans 刺激的内皮细胞（ECs）中，血小板活化、聚集和凝血明显改变，中性粒细胞迁移增加，从而诱导血栓形成。变形链球菌刺激显著增强血小板和肿瘤细胞与炎症内皮细胞的黏附。此外，S. mutans 诱导的肺血栓形成促进体内乳腺癌细胞向肺部转移，而抗血小板药物阿司匹林可减少这种转移。我们的研究结果表明，口腔细菌通过血栓形成促进肿瘤转移。口腔健康管理对于预防 CVD、肿瘤转移及其相关死亡非常重要。
