Development of Immortalized Human Tumor Endothelial Cells from Renal Cancer
by
Nako Maishi 1,2,3,†, Hiroshi Kikuchi 2,4,†, Masumi Sato 2, Hiroko Nagao-Kitamoto 3, Dorcas A. Annan 1,2, Shogo Baba 1, Takayuki Hojo 2,3,5, Misa Yanagiya 2,6, Yusuke Ohba 7, Genichiro Ishii 8, Kenkichi Masutomi 9, Nobuo Shinohara 4, Yasuhiro Hida 10 and Kyoko Hida 1,2,3,*
Nako Maishi 1,2,3,†, Hiroshi Kikuchi 2,4,†, Masumi Sato 2, Hiroko Nagao-Kitamoto 3, Dorcas A. Annan 1,2, Shogo Baba 1, Takayuki Hojo 2,3,5, Misa Yanagiya 2,6, Yusuke Ohba 7, Genichiro Ishii 8, Kenkichi Masutomi 9, Nobuo Shinohara 4, Yasuhiro Hida 10 and Kyoko Hida 1,2,3,*
1
Vascular Biology and Molecular Pathology, Hokkaido University Graduate School of Dental Medicine, Sapporo 060-8586, Japan
2
Vascular Biology, Frontier Research Unit, Institute for Genetic Medicine, Hokkaido University, Sapporo 060-0815, Japan
3
Department of Vascular Biology, Hokkaido University Graduate School of Dental Medicine, Sapporo 060-8586, Japan
4
Department of Renal and Genitourinary Surgery, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan
5
Department of Dental Anesthesiology, Hokkaido University Graduate School of Dental Medicine, Sapporo 060-8586, Japan
6
Department of Oral Diagnosis and Medicine, Hokkaido University Graduate School of Dental Medicine, Sapporo 060-8586, Japan
7
Department of Cell Physiology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo 060-8638, Japan
8
Division of Pathology, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Kashiwa 277-8577, Japan
9
Division of Cancer Stem Cell, National Cancer Center Research Institute, Tokyo 104-0045, Japan
10
Department of Cardiovascular and Thoracic Surgery, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Int. J. Mol. Sci. 2019, 20(18), 4595; https://doi.org/10.3390/ijms20184595
Received: 11 July 2019 / Revised: 13 September 2019 / Accepted: 13 September 2019 / Published: 17 September 2019
(This article belongs to the Special Issue Advanced Research on Tumor Endothelial Cells)
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.
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MDPI and ACS Style
Maishi, N.; Kikuchi, H.; Sato, M.; Nagao-Kitamoto, H.; Annan, D.A.; Baba, S.; Hojo, T.; Yanagiya, M.; Ohba, Y.; Ishii, G.; Masutomi, K.; Shinohara, N.; Hida, Y.; Hida, K. Development of Immortalized Human Tumor Endothelial Cells from Renal Cancer. Int. J. Mol. Sci. 2019, 20, 4595.
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