Related Experiment Video
Updated: Jan 19, 2026
Microfluidic Co-culture of Renal Healthy and Tumor Epithelium to Model Kidney Cancer Progression
Published on: January 31, 2025
Development of Immortalized Human Tumor Endothelial Cells from Renal Cancer
Nako Maishi1,2,3, Hiroshi Kikuchi4,5, Masumi Sato6
1Vascular Biology and Molecular Pathology, Hokkaido University Graduate School of Dental Medicine, Sapporo 060-8586, Japan. mnako@den.hokudai.ac.jp.
Abstract:
Tumor angiogenesis research and antiangiogenic drug development make use of cultured endothelial cells (ECs) including the human microvascular ECs among others. However, it has been reported that tumor ECs (TECs) are different from normal ECs (NECs). To functionally validate antiangiogenic drugs, cultured TECs are indispensable tools, but are not commercially available. Primary human TECs are available only in small quantities from surgical specimens and have a short life span in vitro due to their cellular senescence. We established immortalized human TECs (h-imTECs) and their normal counterparts (h-imNECs) by infection with lentivirus producing simian virus 40 large T antigen and human telomerase reverse transcriptase to overcome the replication barriers. These ECs exhibited an extended life span and retained their characteristic endothelial morphology, expression of endothelial marker, and ability of tube formation. Furthermore, h-imTECs showed their specific characteristics as TECs, such as increased proliferation and upregulation of TEC markers. Treatment with bevacizumab, an antiangiogenic drug, dramatically decreased h-imTEC survival, whereas the same treatment failed to alter immortalized NEC survival. Hence, these h-imTECs could be a valuable tool for drug screening to develop novel therapeutic agents specific to TECs or functional biological assays in tumor angiogenesis research.
Insights
Researchers developed immortalized human tumor endothelial cells (h-imTECs) for studying tumor angiogenesis. These cells are crucial for developing and testing antiangiogenic drugs targeting tumor vasculature.
Area of Science:
- Oncology
- Cell Biology
- Drug Development
Background:
- Tumor angiogenesis research relies on endothelial cells (ECs), but tumor ECs (TECs) differ from normal ECs (NECs).
- Cultured TECs are vital for antiangiogenic drug validation but are scarce and senesce quickly.
- Immortalized cell lines are needed to overcome limitations of primary cells.
Purpose of the Study:
- To establish immortalized human TECs (h-imTECs) and normal ECs (h-imNECs).
- To validate h-imTECs as a model for studying tumor-specific endothelial cell characteristics.
- To assess the utility of h-imTECs for antiangiogenic drug screening.
Main Methods:
- Immortalization of human TECs and NECs using lentiviral vectors encoding SV40 large T antigen and hTERT.
- Characterization of immortalized cells for morphology, endothelial markers, proliferation, and tube formation.
- Assessment of h-imTEC response to bevacizumab treatment compared to h-imNECs.
Main Results:
- Established immortalized h-imTECs and h-imNECs with extended lifespan and retained endothelial characteristics.
- h-imTECs demonstrated specific tumor-associated features, including increased proliferation and marker expression.
- Bevacizumab significantly reduced h-imTEC survival, while h-imNEC survival remained unaffected.
Conclusions:
- Immortalized h-imTECs serve as a valuable and reproducible model for tumor angiogenesis research.
- h-imTECs are suitable for functional assays and drug screening of antiangiogenic therapies.
- This model facilitates the development of novel therapeutic agents targeting tumor vasculature.
