@article{63aefdbf70d648d59bc41b21e670b2c5,
title = "Antitumor effects of novel mAbs against cationic amino acid transporter 1 (CAT1) on human CRC with amplified CAT1 gene",
abstract = "Copy number alterations detected by comparative genomic hybridization (CGH) can lead to the identification of novel cancer-related genes. We analyzed chromosomal aberrations in a set of 100 human primary colorectal cancers (CRCs) using CGH and found a solute carrier (SLC) 7A1 gene, which encodes cationic amino acid transporter 1 (CAT1) with 14 putative transmembrane domains, in a chromosome region (13q12.3) with a high frequency of gene amplifications. SLC7A1/CAT1 is a transporter responsible for the uptake of cationic amino acids (arginine, lysine, and ornithine) essential for cellular growth. Microarray and PCR analyses have revealed that mRNA transcribed from CAT1 is overexpressed in more than 70% of human CRC samples, and RNA interference–mediated knockdown of CAT1 inhibited the cell growth of CRCs. Rats were immunized with rat hepatoma cells expressing CAT1 tagged with green fluorescent protein (GFP), and rat splenocytes were fused with mouse myeloma cells. Five rat monoclonal antibodies (mAbs) (CA1 ~ CA5) reacting with HEK293 cells expressing CAT1-GFP in a GFP expression–dependent manner were selected from established hybridoma clones. Novel anti-CAT1 mAbs selectively reacted with human CRC tumor tissues compared with adjacent normal tissues according to immuno-histochemical staining and bound strongly to numerous human cancer cell lines by flow cytometry. Anti-CAT1 mAbs exhibited internalization activity, antibody-dependent cellular cytotoxicity, and migration inhibition activity against CRC cell lines. Furthermore, CA2 inhibited the in vivo growth of human HT29 and SW-C4 CRC tumors in nude mice. This study suggested CAT1 to be a promising target for mAb therapy against CRCs.",
keywords = "CAT1, CRC, SLC7A1, mAb, oncogene addiction",
author = "Kouki Okita and Yuta Hara and Hiroshi Okura and Hidemi Hayashi and Yoko Sasaki and Sachiko Masuko and Eri Kitadai and Kazue Masuko and Soshi Yoshimoto and Natsumi Hayashi and Reiko Sugiura and Yuichi Endo and Shogo Okazaki and Sayaka Arai and Toshiaki Yoshioka and Toshiharu Matsumoto and Yasutaka Makino and Hiromitsu Komiyama and Kazuhiro Sakamoto and Takashi Masuko",
note = "Funding Information: This study was supported by the MEXT‐Supported Program for the Strategic Research Foundation at Private Universities, 2014–2018 (S1411037 to Sugiura R) and by Grant‐in‐Aid for Scientific Research from the Japan Society for the Promotion of Science (JSPS, KAKENHI), 2016‐2020 (16K10476 to Sakamaoto K). The corresponding author (TM) is deeply grateful to Dr Hamada Y (HAMADA NAIKA CLINIC) for his careful examination and to Dr Yamamoto K (Osaka Hospital, Japan) for the complete endoscopic submucosal dissection of a colon tumor of TM, which was detected in the process of this manuscript preparation. Funding Information: This study was supported by the MEXT-Supported Program for the Strategic Research Foundation at Private Universities, 2014?2018 (S1411037 to Sugiura R) and by Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (JSPS, KAKENHI), 2016-2020 (16K10476 to Sakamaoto K). The corresponding author (TM) is deeply grateful to Dr Hamada Y (HAMADA NAIKA CLINIC) for his careful examination and to Dr Yamamoto K (Osaka Hospital, Japan) for the complete endoscopic submucosal dissection of a colon tumor of TM, which was detected in the process of this manuscript preparation. Publisher Copyright: {\textcopyright} 2020 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",
year = "2021",
month = feb,
doi = "10.1111/cas.14741",
language = "English",
volume = "112",
pages = "563--574",
journal = "Cancer Science",
issn = "1347-9032",
publisher = "Wiley-Blackwell",
number = "2",
}