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Development of Immortalized Human Tumor Endothelial Cells from Renal Cancer.
- Source :
-
International journal of molecular sciences [Int J Mol Sci] 2019 Sep 17; Vol. 20 (18). Date of Electronic Publication: 2019 Sep 17. - Publication Year :
- 2019
-
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.
- Subjects :
- Antigens, Polyomavirus Transforming genetics
Antigens, Polyomavirus Transforming metabolism
Biomarkers
Cell Line, Transformed
Ectopic Gene Expression
Humans
Karyotyping
Telomerase genetics
Telomerase metabolism
Cell Transformation, Neoplastic genetics
Cell Transformation, Neoplastic metabolism
Endothelial Cells metabolism
Endothelial Cells pathology
Kidney Neoplasms pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1422-0067
- Volume :
- 20
- Issue :
- 18
- Database :
- MEDLINE
- Journal :
- International journal of molecular sciences
- Publication Type :
- Academic Journal
- Accession number :
- 31533313
- Full Text :
- https://doi.org/10.3390/ijms20184595