Fang Yingshuai, Cui Wenming, Yang Yabing, Zhang Xinhao, Tian Mengyao, Xie Zhiyuan, Guo Ying, Yuan Weitang, Li Zhen, Yang Shuaixi
The First Clinical School of Medicine, Zhengzhou University, Zhengzhou 450001, China.
Department of Colorectal Surgery, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450000, China.
Theranostics. 2025 May 25;15(13):6454-6475. doi: 10.7150/thno.113665. eCollection 2025.
The premetastatic niche (PMN) represents a metastasis-facilitative microenvironment established prior to tumor dissemination, initiated by vascular leakage and endothelial cell (EC) functional remodeling. ECs play pivotal roles as bridges in different stages of the metastatic cascade. As critical stromal components within the PMN, ECs not only drive angiogenesis but also actively orchestrate immune suppression, extracellular matrix (ECM) remodeling, and the inflammatory signaling characteristic of PMN formation, with multiple specific signaling pathways such as VEGF/Notch playing a crucial role. With the evolving understanding of the role of ECs in controlling tumor metastasis, therapeutic strategies targeting ECs within the PMN, such as antiangiogenic therapy (AAT), targeting of endothelial glycocalyx (GCX), inhibition of tumor-derived exosome (TDE) and angiocrine signaling, are becoming research hotspots. This review systematically delineates the cellular and molecular composition of PMNs, dynamically dissects their spatiotemporal evolution, and highlights organ-specific mechanisms of EC-driven PMN establishment. Furthermore, we summarize emerging EC-targeted therapeutic strategies, providing innovative insights for inhibiting tumor metastasis.
前转移生态位（PMN）代表肿瘤播散之前建立的促进转移的微环境，由血管渗漏和内皮细胞（EC）功能重塑引发。内皮细胞在转移级联反应的不同阶段作为桥梁发挥关键作用。作为PMN内关键的基质成分，内皮细胞不仅驱动血管生成，还积极协调免疫抑制、细胞外基质（ECM）重塑以及PMN形成的炎症信号传导，多种特定信号通路如VEGF/Notch发挥着关键作用。随着对内皮细胞在控制肿瘤转移中作用的认识不断深入，针对PMN内内皮细胞的治疗策略，如抗血管生成治疗（AAT）、靶向内皮糖萼（GCX）、抑制肿瘤衍生外泌体（TDE）和血管分泌信号传导，正成为研究热点。本综述系统地描绘了PMN的细胞和分子组成，动态剖析了它们的时空演变，并突出了内皮细胞驱动的PMN建立的器官特异性机制。此外，我们总结了新兴的内皮细胞靶向治疗策略，为抑制肿瘤转移提供创新见解。
