Shang Haotian, Zhang Yumin, Chao Tengfei
Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Int J Mol Sci. 2025 Jun 6;26(12):5430. doi: 10.3390/ijms26125430.
Breast cancer metastasis remains the primary driver of patient mortality, involving dynamic interactions between tumor cells and distant organ microenvironments. In recent years, tumor cell-derived extracellular vesicles (EVs) have emerged as critical information carriers, playing central roles in breast cancer metastasis by mediating organ-specific pre-metastatic niche formation, immune modulation, and tumor cell adaptive evolution. Studies have demonstrated that EVs drive the metastatic cascade through the delivery of bioactive components, including nucleic acids (e.g., miRNAs, circRNAs), proteins (e.g., integrins, metabolic enzymes), and lipids, which collectively regulate osteoclast activation, immune cell polarization, vascular permeability alterations, and extracellular matrix (ECM) remodeling in target organs such as bone, the lungs, and the liver. Molecular heterogeneity in EVs derived from different breast cancer subtypes strongly correlates with organotropism, providing potential biomarkers for metastasis prediction. Leveraging the organotrophic mechanisms of EVs and their dual regulatory roles in metastasis (pro-metastatic and anti-metastatic), strategies targeting EV biogenesis, cargo loading, or delivery exhibits translational potential in diagnostics and therapeutics. In this review, we summarize recent advances in understanding the role of breast cancer-derived exosomes in mediating metastatic organotropism and discuss the potential clinical applications of targeting exosomes as novel diagnostic and therapeutic strategies for breast cancer.
乳腺癌转移仍然是患者死亡的主要驱动因素,涉及肿瘤细胞与远处器官微环境之间的动态相互作用。近年来,肿瘤细胞衍生的细胞外囊泡(EVs)已成为关键的信息载体,通过介导器官特异性的转移前生态位形成、免疫调节和肿瘤细胞适应性进化,在乳腺癌转移中发挥核心作用。研究表明,EVs通过传递生物活性成分驱动转移级联反应,这些生物活性成分包括核酸(如miRNAs、circRNAs)、蛋白质(如整合素、代谢酶)和脂质,它们共同调节骨、肺和肝等靶器官中的破骨细胞活化、免疫细胞极化、血管通透性改变和细胞外基质(ECM)重塑。来自不同乳腺癌亚型的EVs中的分子异质性与器官嗜性密切相关,为转移预测提供了潜在的生物标志物。利用EVs的器官营养机制及其在转移中的双重调节作用(促转移和抗转移),针对EV生物发生、货物装载或递送的策略在诊断和治疗方面具有转化潜力。在本综述中,我们总结了在理解乳腺癌来源的外泌体在介导转移器官嗜性中的作用方面的最新进展,并讨论了将靶向外泌体作为乳腺癌新型诊断和治疗策略的潜在临床应用。
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