Oral bacterium Streptococcus mutans promotes tumor metastasis through thrombosis formation

Author:

Yu Li1ORCID,Hong Yuying12,Maishi Nako1,Matsuda Aya Yanagawa1,Hida Yasuhiro3ORCID,Hasebe Akira4,Kitagawa Yoshimasa2,Hida Kyoko1ORCID

Affiliation:

1. Vascular Biology and Molecular Pathology, Faculty of Dental Medicine and Graduate School of Dental Medicine Hokkaido University Sapporo Japan

2. Oral Diagnosis and Medicine, Faculty of Dental Medicine and Graduate School of Dental Medicine Hokkaido University Sapporo Japan

3. Advanced Robotic and Endoscopic Surgery, School of Medicine Fujita Health University Toyoake Japan

4. Oral Molecular Microbiology, Faculty of Dental Medicine and Graduate School of Dental Medicine Hokkaido University Sapporo Japan

Abstract

AbstractThrombosis 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.

Funder

Japan Agency for Medical Research and Development

Japan Society for the Promotion of Science

Publisher

Wiley

Subject

Cancer Research,Oncology,General Medicine

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