Tumor-resident intracellular microbiota promotes metastatic colonization in breast cancer

Aikun Fu; Bingqing Yao; Tingting Dong; Yongyi Chen; Jia Yao; Yu Liu; Hang Li; Huiru Bai; Xiaoqin Liu; Yue Zhang; Chunhui Wang; Yajing Guo; Nan Li; Shang Cai

doi:10.1016/j.cell.2022.02.027

Tumor-resident intracellular microbiota promotes metastatic colonization in breast cancer

Cell. 2022 Apr 14;185(8):1356-1372.e26. doi: 10.1016/j.cell.2022.02.027. Epub 2022 Apr 7.

Authors

Aikun Fu¹, Bingqing Yao², Tingting Dong², Yongyi Chen³, Jia Yao⁴, Yu Liu⁴, Hang Li⁵, Huiru Bai², Xiaoqin Liu⁶, Yue Zhang², Chunhui Wang⁷, Yajing Guo⁸, Nan Li⁵, Shang Cai⁹

Affiliations

¹ Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, Zhejiang, China; School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China; Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China; Institute of Biology, Westlake Institute for Advanced Study, Hangzhou, Zhejiang Province, China.
² School of Life Sciences, Fudan University, Shanghai, China; Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, Zhejiang, China; School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China; Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China.
³ Department of Clinical Laboratory, Zhejiang Cancer Hospital, Hangzhou, Zhejiang Province, 310000, China.
⁴ Department of Breast Surgery, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China.
⁵ Westlake University High-Performance Computing Center, Westlake University, Hangzhou, Zhejiang, China.
⁶ Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, Zhejiang, China; School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China; Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China; School of Life Sciences, Fudan University, Shanghai, China.
⁷ Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, Zhejiang, China; School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China; Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China; Westlake Disease Modeling lab, Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, Zhejiang, China.
⁸ Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, Zhejiang, China; School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China; Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China.
⁹ Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, Zhejiang, China; School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China; Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China; Westlake Disease Modeling lab, Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, Zhejiang, China; Institute of Biology, Westlake Institute for Advanced Study, Hangzhou, Zhejiang Province, China. Electronic address: [email protected].

PMID: 35395179
DOI: 10.1016/j.cell.2022.02.027

Abstract

Tumor-resident intracellular microbiota is an emerging tumor component that has been documented for a variety of cancer types with unclear biological functions. Here, we explored the functional significance of these intratumor bacteria, primarily using a murine spontaneous breast-tumor model MMTV-PyMT. We found that depletion of intratumor bacteria significantly reduced lung metastasis without affecting primary tumor growth. During metastatic colonization, intratumor bacteria carried by circulating tumor cells promoted host-cell survival by enhancing resistance to fluid shear stress by reorganizing actin cytoskeleton. We further showed that intratumor administration of selected bacteria strains isolated from tumor-resident microbiota promoted metastasis in two murine tumor models with significantly different levels of metastasis potential. Our findings suggest that tumor-resident microbiota, albeit at low biomass, play an important role in promoting cancer metastasis, intervention of which might therefore be worth exploring for advancing oncology care.

Keywords: breast cancer metastasis; circulating tumor cells; cytoskeleton reorganization; fluid shear stress; intracellular bacteria; intratumor microbiota; metastatic colonization.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Breast Neoplasms* / microbiology
Breast Neoplasms* / pathology
Cell Line, Tumor
Female
Humans
Lung Neoplasms / pathology
Mice
Microbiota*
Neoplasm Metastasis*
Neoplastic Cells, Circulating / pathology