Tumour endothelial cells in cancer: Chemo-physical crosstalk and angiogenic signalling in the tumour microenvironment

The tumour microenvironment (TME) represents a complex, dynamic ecosystem comprising cellular and acellular elements that collectively facilitate tumour progression, invasion, and metastasis through intricate chemo-mechanical interactions. Cancer cells drive TME remodelling by recruiting and reprogramming stromal components, including cancer-associated fibroblasts (CAFs) that alter extracellular matrix (ECM) composition and stiffness, tumour-associated macrophages (TAMs) that promote immunosuppressive conditions, and tumour endothelial cells (TECs) that establish aberrant vascular networks. This review synthesises current literature on the pivotal role of TECs in tumour angiogenesis, emphasising their bidirectional crosstalk with cancer and stromal cells via chemical signals (e.g., growth factors under hypoxia) and mechanical cues (e.g., ECM stiffness and topography) that modulate cellular contractility, adhesion, and biochemical release. Key findings reveal how TECs integrate these multifaceted stimuli to orchestrate vascular remodelling, enhance permeability, and foster metastatic dissemination, often through dysregulated pathways distinct from normal endothelium. Ultimately, elucidating these mechanisms offers promising avenues for developing targeted therapies that selectively inhibit TEC-mediated angiogenesis while preserving physiological vascular function.