Title: | Development of Immortalized Human Tumor Endothelial Cells from Renal Cancer |
Authors: | Maishi, Nako Browse this author →KAKEN DB |
Kikuchi, Hiroshi Browse this author |
Sato, Masumi Browse this author |
Nagao-Kitamoto, Hiroko Browse this author |
Annan, Dorcas A. Browse this author |
Baba, Shogo Browse this author |
Hojo, Takayuki Browse this author →KAKEN DB |
Yanagiya, Misa Browse this author |
Ohba, Yusuke Browse this author →KAKEN DB |
Ishii, Genichiro Browse this author |
Masutomi, Kenkichi Browse this author |
Shinohara, Nobuo Browse this author →KAKEN DB |
Hida, Yasuhiro Browse this author →KAKEN DB |
Hida, Kyoko Browse this author →KAKEN DB |
Keywords: | immortalization |
tumor endothelial cells |
angiogenesis |
renal carcinoma |
Issue Date: | 2-Sep-2019 |
Publisher: | MDPI |
Journal Title: | International Journal of Molecular Sciences |
Volume: | 20 |
Issue: | 18 |
Start Page: | 4595 |
Publisher DOI: | 10.3390/ijms20184595 |
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. |
Rights: | © 2019 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/). |
http://creativecommons.org/licenses/by/4.0/ |
Type: | article |
URI: | http://hdl.handle.net/2115/76183 |
Appears in Collections: | 歯学院・歯学研究院 (Graduate School of Dental Medicine / Faculty of Dental Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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