Molecular insights into the role of tumor-specific endothelial cells in metastasis

Abstract

Tumor-specific endothelial cells (TECs) play a crucial role in tumor advancement, metastasis, and immune evasion, distinguishing themselves from normal endothelial cells (NECs) through unique gene expression and enhanced pro-angiogenic signaling. TECs facilitate metastasis by increasing vascular permeability and supporting tumor angiogenesis, while also aiding immune evasion via the expression of checkpoint molecules, such as PD-L1, which dampen T cell activity. Targeting TECs shows promise for improving cancer therapy. Anti-angiogenic treatments, including VEGF inhibitors like bevacizumab, aim to reduce tumor vascularity. Still, TECs can develop resistance through alternative signaling pathways, necessitating combination therapies that involve agents targeting FGF and PDGF. Immune checkpoint inhibitors, such as anti-PD-1 and anti-PD-L1 antibodies, can enhance immune responses when combined with anti-angiogenic treatments. Furthermore, targeting TEC-related pathways, such as TGF-β and Angiopoietin-2, may stabilize tumor vasculature and limit metastasis. Given the heterogeneity of TECs, multi-targeted approaches integrating anti-angiogenic and immune-modulating therapies are crucial. Advances in single-cell transcriptomics and proteomics will refine TEC-targeted treatments, supporting precision medicine in oncology. This review highlights the therapeutic potential of TECs and explores innovative strategies for enhancing cancer treatment outcomes.

Keywords: Angiogenesis; Cancer; Immune Checkpoint Blockade; Immune Evasion; Metastasis; Tumor microenvironment; Tumor-specific Endothelial Cells.