Locally producing antibacterial peptide to deplete intratumoral pathogen for preventing metastatic breast cancer  

作　　者：Shizhen Geng Tingting Xiang Yaru Shi Mengnian Cao Danyu Wang Jing Wang Xinling Li Haiwei Song Zhenzhong Zhang Jinjin Shi Junjie Liu Airong Li Ke Sun 

机构地区：[1]Department of Urinary Surgery,the First Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,China [2]School of Pharmaceutical Sciences,Zhengzhou University,Zhengzhou 450001,China

出　　处：《Acta Pharmaceutica Sinica B》2025年第2期1084-1097,共14页药学学报(英文版)

基　　金：supported by the National Natural Science Foundation of China(82172762,21904119,and 82073395);Science and technology innovation talents support project of Henan Province(23HASTIT041);Henan Science Fund for Outstanding Young Scholars(232300421051,China).

摘　　要：Metastatic dissemination is the major cause of death from breast-cancer(BC).Fusobacterium nucleatum(F.n)is widely enriched in BC and has recently been identified as one of the high-risk factors for promoting BC metastasis.Here,with an experimental model,we demonstrated that intratumoral F.n induced BC aggressiveness by transcriptionally activating Epithelial-mesenchymal transition-associated genes.Therefore,the F.n may be a potential target to prevent metastasis.Given the fact that cancer-associated fibroblasts(CAFs)are abundant in BC and located near blood vessels,we report an optogenetic system that drives CAF to in situ produce human antibacterial peptide LL37,with the characteristics of biosafety and freely intercellular trafficking,for depleting intratumoral F.n,leading to a 72.1%reduction in lung metastatic nodules number without affecting the balance of the systemic flora.Notably,mild photothermal treatment was found that could normalize CAF,contributing to synergistically inhibiting BC metastasis.In addition,the system can also simultaneously encode a gene of TNF-related apoptosis-inducing ligand to suppress the primary tumor.Together,our study highlights the potential of local elimination of tumor pathogenic bacteria to prevent BC metastasis.

关 键 词：Intratumoral pathogen METASTASIS Antibacterial peptide OPTOGENETICS Breast cancer Fusobacterium nucleatum Cancer-associated fibroblast Mild heat 

分 类 号：R737.9[医药卫生—肿瘤]