This approach diverges from traditional models of tumor vasculature by showing that a subset of cells within the tumor can directly assume and maintain an endothelial identity. Unlike vasculogenic mimicry—where aggressive tumor cells form vessel-like channels temporarily—the tTAECs described here are cell-autonomous, genetically distinct from host endothelium, and capable of long-term proliferation if immortalized. Their durable functionality and human-only chromosomal profile highlight a novel target for anti-angiogenic therapies, offering a new avenue for disrupting the blood supply that sustains tumor growth.
Description
Tumor-associated endothelial cells (TAECs) were isolated from four different cancer cell lines. Human cancer cells engineered with multiple genetic tags are implanted into mice to produce xenograft tumors, from which endothelial-like cells (tTAECs) are isolated. These tTAECs carry only the human tumor genome, exhibit classic endothelial morphology, express specific vascular markers, and form capillary-like structures in vitro. After several passages, they enter a senescent-like arrest but can be rendered long-lived by introducing telomerase. When nonimmortalized tTAECs are reintroduced into animals, they autonomously integrate into tumor blood vessels, demonstrating a stable endothelial phenotype that persists in vivo without evidence of cell fusion or transient mimicry.
Applications
Anti-angiogenic drug screening
Preclinical tumor vasculature modeling
Personalized cancer therapy testing
Telomerase-inhibitor evaluation
Diagnostic biomarker development
Advantages
Enables isolation of pure tumor-derived endothelial cells for detailed study of tumor angiogenesis
Provides a durable in vitro and in vivo model (via telomerase-immortalized tTAECs) for anti-angiogenic drug screening
Clarifies mechanisms of vasculogenic mimicry and tumor cell plasticity, advancing understanding of tumor vascular biology
Highlights tumor-specific genomic abnormalities in the vasculature, guiding development of more selective anti-angiogenic therapies
Offers novel biomarkers for monitoring tumor progression and assessing treatment response
