Journal Article Review Epublish
PubMed: 40521189 DOI: 10.7150/thno.113665
Breaking the premetastatic niche barrier: the role of endothelial cells and therapeutic strategies.
Theranostics 15(13):6454-6475
Authors: Yingshuai Fang, Wenming Cui, Yabing Yang, Xinhao Zhang, Mengyao Tian, Zhiyuan Xie, Ying Guo, Weitang Yuan, Zhen Li, Shuaixi Yang
Affiliations
- 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.
Abstract
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.
MeSH
Cells, Nanomedicine, Neoplasms, Neoplasm Metastasis, Endothelial Cells, Therapeutics