RRC ID 67106
Author Maishi N, Kikuchi H, Sato M, Nagao-Kitamoto H, Annan DA, Baba S, Hojo T, Yanagiya M, Ohba Y, Ishii G, Masutomi K, Shinohara N, Hida Y, Hida K.
Title Development of Immortalized Human Tumor Endothelial Cells from Renal Cancer.
Journal Int J Mol Sci
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.
Volume 20(18)
Published 2019-9-17
DOI 10.3390/ijms20184595
PII ijms20184595
PMID 31533313
PMC PMC6770423
MeSH Antigens, Polyomavirus Transforming / genetics Antigens, Polyomavirus Transforming / metabolism Biomarkers Cell Line, Transformed Cell Transformation, Neoplastic* / genetics Cell Transformation, Neoplastic* / metabolism Ectopic Gene Expression Endothelial Cells / metabolism* Endothelial Cells / pathology* Humans Karyotyping Kidney Neoplasms / pathology* Telomerase / genetics Telomerase / metabolism
IF 4.556
Resource
Human and Animal Cells 293T(RCB2202)