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Please use this identifier to cite or link to this item: http://hdl.handle.net/10564/3186

Title: Pro-chemotherapeutic effects of antibody against extracellular domain of claudin-4 in bladder cancer.
Other Titles: 膀胱癌における抗クローディン4細胞外ドメイン中和抗体の化学療法増感効果
Authors: Kuwada, Masaomi
Chihara, Yoshitomo
Luo, Yi
Li, Xiangru
Nishiguchi, Yukiko
Fujiwara, Rina
Sasaki, Takamistu
Fujii, Kiyomu
Ohmori, Hitoshi
Fujimoto, Kiyohide
Kondoh, Masuo
Kuniyasu, Hiroki
Keywords: Claudin
Tight junction
Antibody therapy
Microenvironment
Issue Date: 1-Dec-2015
Publisher: Elsevier
Citation: Cancer letters Vol.369 No.1 p.212-221(2015.12)
Abstract: Bladder cancer displays an aggressive phenotype in the muscle-invasive phase, and is associated with a high mortality rate. Therefore, novel molecular therapeutic targets are needed to improve patient survival. A monoclonal antibody against the extracellular domain of the claudin-4 (CLDN4) tight junction protein was established by immunizing rats with a plasmid vector encoding human CLDN4. A hybridoma clone, producing a rat monoclonal antibody recognizing CLDN4 (clone 4D3), was obtained. Immunohistochemistry by using the 4D3 antibody showed that CLDN4 expression was associated with local invasion, nodal metastasis, distant metastasis, and advanced stage in 86 cases of bladder cancer. The 4D3 antibody inhibited growth, invasion, and survival, associated with abrogation of the intratumoral microenvironment; lowered concentrations of epidermal growth factor and vascular endothelial growth factor were found in three-dimensional cultures of T24 and RT4 cells. In combination with cisplatin therapy, 4D3 enhanced cisplatin cytotoxicity by increasing cellular permeability, leading to increased intracellular cisplatin concentrations. In mouse models of subcutaneous tumors and lung metastasis, 4D3 enhanced tumor growth inhibition, alone and with concurrent cisplatin treatment. The anti-tumor activity of the newly established 4D3 antibody suggests that it may be a powerful tool in CLDN4-targeting therapy, and in combination with chemotherapy.
Description: 博士(医学)・甲第649号・平成28年3月15日
Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
URI: http://hdl.handle.net/10564/3186
ISSN: 03043835
Academic Degrees and number: 24601A649
Degree-granting date: 2016-03-15
Degree name: 博士(医学)
Degree-granting institutions: 奈良県立医科大学
Appears in Collections:2015年度

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