Potential role of intratumoral Fusobacterium nucleatum and interleukin-1 beta in breast cancer cell growth

Chun-Ming Chang; Long Yin Lam; Ho Yin Pekkle Lam; Pin-Ying Kao; Shih-Ting Hsu; Wen-Jui Wu; Kai-Chih Chang; Chih-Yang Huang

doi:10.1016/j.jmii.2025.05.008

Potential role of intratumoral Fusobacterium nucleatum and interleukin-1 beta in breast cancer cell growth

J Microbiol Immunol Infect. 2025 Jun 7:S1684-1182(25)00119-7. doi: 10.1016/j.jmii.2025.05.008. Online ahead of print.

Authors

Chun-Ming Chang¹, Long Yin Lam², Ho Yin Pekkle Lam³, Pin-Ying Kao⁴, Shih-Ting Hsu⁵, Wen-Jui Wu⁵, Kai-Chih Chang⁶, Chih-Yang Huang⁷

Affiliations

¹ Department of General Surgery, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan; Institute of Medical Sciences, Tzu Chi University, Hualien, Taiwan; School of Medicine, Tzu Chi University, Hualien, Taiwan.
² State Key Laboratory of Chemical Biology and Drug Discovery, Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Kowloon, Hong Kong SAR, China.
³ Institute of Medical Sciences, Tzu Chi University, Hualien, Taiwan; Department of Biochemistry, School of Medicine, Tzu Chi University, Hualien, Taiwan; Master Program in Biomedical Science, School of Medicine, Tzu Chi University, Hualien, Taiwan. Electronic address: pekklelavabo@mail.tcu.edu.tw.
⁴ Department of Laboratory Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan.
⁵ Department of Laboratory Medicine and Biotechnology, Tzu Chi University, Hualien, Taiwan.
⁶ Department of Laboratory Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan; Department of Laboratory Medicine and Biotechnology, Tzu Chi University, Hualien, Taiwan.
⁷ Institute of Medical Sciences, Tzu Chi University, Hualien, Taiwan; Cardiovascular and Mitochondria Related Disease Research Center, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan; Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan; Center of General Education, Buddhist Tzu Chi Medical Foundation, Tzu Chi University of Science and Technology, Hualien, Taiwan; Graduate Institute of Basic Medical Science, China Medical University, Taichung City, Taiwan.

PMID: 40506319
DOI: 10.1016/j.jmii.2025.05.008

Abstract

Background: It has been shown that the human breast harbors a rich and diverse microbiome, with significant differences observed between tumor tissue and normal breast tissue. Recently, Fusobacterium nucleatum (F. nucleatum) has been shown to affect breast cancer growth, but the underlying mechanism remains enigmatic.

Methods: Breast cancer tissues were obtained from clinical patients and analyzed for the microbiome composition using 16S rDNA sequencing and qPCR. Both serum and intratumoral cytokine levels were measured to assess their correlation with intratumoral F. nucleatum. Breast cancer cell lines and patient-derived cancer cells were infected with different strains of F. nucleatum, followed by different analyses. Additionally, peripheral blood mononuclear cells (PBMCs) were isolated from healthy individuals to investigate the immunoregulatory effect of F. nucleatum.

Results: Our results identified a higher abundance of F. nucleatum in breast cancer tissue compared to adjacent normal breast tissue, which strongly correlated with intratumoral IL-1β levels. In vitro studies confirmed this correlation, demonstrating that infection of breast cancer cells with F. nucleatum promotes tumor growth. Further investigation suggested that F. nucleatum induces IL-1β secretion in both breast cancer cells and PBMCs, but only IL-1β secreted by breast cancer cells stimulates cancer cell growth. Inhibition of NLRP3 reversed the growth-promoting effect of F. nucleatum on breast cancer cells.

Conclusion: Our results demonstrate the role of F. nucleatum in stimulating breast cancer cell growth. Therefore, targeting intratumoral F. nucleatum could provide a promising therapeutic approach to combat breast cancer.

Keywords: Breast cancer; Fusobacterium nucleatum; Interleukin-1 beta; Intratumoral microbiome.