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Development of Immortalized Human Tumor Endothelial Cells from Renal Cancer

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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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