Tumor-derived Cav-1 promotes pre-metastatic niche formation and lung metastasis in breast cancer

作者：Yi Wang, Yuqiu Li, Junpei Zhong, Miao Li, Youjia Zhou, Lin Qing, Siwen Zong, Wenting Luo, Jiayang Wang, Keqin Wang, Jie Wang, Lixia Xiong · 发表于：Theranostics · 年份：2023 · DOI：10.7150/thno.79250 · 被引用次数：103 · 研究领域：Extracellular vesicles in disease、Caveolin-1 and cellular processes、MicroRNA in disease regulation

Rationale: Breast cancer (BC), as one of the most frequently diagnosed cancer, has a poor prognosis due to the development of distant metastasis.Among the BC metastatic sites, lung is one of the most common sites.Caveolin-1 (Cav-1) is a functional membrane protein that plays a vital role in tumor metastasis.Although studies have revealed that Cav-1 levels were elevated in patients with advanced cancer, whether Cav-1 affects BC lung metastasis by influencing the formation of pre-metastatic niche (PMN) through exosomes has not been explored.Methods: Differential ultracentrifugation, transmission electron microscopy and nanoparticle tracking analysis were used to verify the presence of exosomes.Transwell assays were used to examine the biological effects of exosomes containing Cav-1.Both in vitro cell cultures and mammary tumor cell-induced mouse models were used to assess the lung metastasis.The regulatory mechanisms of PMN formation were revealed using western blot, flow cytometry, RT-qPCR, immunofluorescence assays, gene overexpression assays and RNA interference assays.Results: Exosomes have critical functions in transporting Cav-1 between primary BC and metastatic organ microenvironments.Cav-1 in BC-derived exosomes can act as a signaling molecule to mediate intercellular communication and regulate the PMN before lung metastasis by regulating the expression of PMN marker genes and inflammatory chemokines in lung epithelial cells, promoting the secretion of tenascin-C (TnC) ...