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HEG1 is a novel mucin-like membrane protein that serves as a diagnostic and therapeutic target for malignant mesothelioma

The absence of highly specific markers for malignant mesothelioma (MM) has served an obstacle for its diagnosis and development of molecular-targeting therapy against MM. Here, we show that a novel mucin-like membrane protein, sialylated protein HEG homolog 1 (HEG1), is a highly specific marker for...

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Autores principales: Tsuji, Shoutaro, Washimi, Kota, Kageyama, Taihei, Yamashita, Makiko, Yoshihara, Mitsuyo, Matsuura, Rieko, Yokose, Tomoyuki, Kameda, Yoichi, Hayashi, Hiroyuki, Morohoshi, Takao, Tsuura, Yukio, Yusa, Toshikazu, Sato, Takashi, Togayachi, Akira, Narimatsu, Hisashi, Nagasaki, Toshinori, Nakamoto, Kotaro, Moriwaki, Yasuhiro, Misawa, Hidemi, Hiroshima, Kenzo, Miyagi, Yohei, Imai, Kohzoh
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5374711/
https://www.ncbi.nlm.nih.gov/pubmed/28361969
http://dx.doi.org/10.1038/srep45768
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author Tsuji, Shoutaro
Washimi, Kota
Kageyama, Taihei
Yamashita, Makiko
Yoshihara, Mitsuyo
Matsuura, Rieko
Yokose, Tomoyuki
Kameda, Yoichi
Hayashi, Hiroyuki
Morohoshi, Takao
Tsuura, Yukio
Yusa, Toshikazu
Sato, Takashi
Togayachi, Akira
Narimatsu, Hisashi
Nagasaki, Toshinori
Nakamoto, Kotaro
Moriwaki, Yasuhiro
Misawa, Hidemi
Hiroshima, Kenzo
Miyagi, Yohei
Imai, Kohzoh
author_facet Tsuji, Shoutaro
Washimi, Kota
Kageyama, Taihei
Yamashita, Makiko
Yoshihara, Mitsuyo
Matsuura, Rieko
Yokose, Tomoyuki
Kameda, Yoichi
Hayashi, Hiroyuki
Morohoshi, Takao
Tsuura, Yukio
Yusa, Toshikazu
Sato, Takashi
Togayachi, Akira
Narimatsu, Hisashi
Nagasaki, Toshinori
Nakamoto, Kotaro
Moriwaki, Yasuhiro
Misawa, Hidemi
Hiroshima, Kenzo
Miyagi, Yohei
Imai, Kohzoh
author_sort Tsuji, Shoutaro
collection PubMed
description The absence of highly specific markers for malignant mesothelioma (MM) has served an obstacle for its diagnosis and development of molecular-targeting therapy against MM. Here, we show that a novel mucin-like membrane protein, sialylated protein HEG homolog 1 (HEG1), is a highly specific marker for MM. A monoclonal antibody against sialylated HEG1, SKM9-2, can detect even sarcomatoid and desmoplastic MM. The specificity and sensitivity of SKM9-2 to MM reached 99% and 92%, respectively; this antibody did not react with normal tissues. This accurate discrimination by SKM9-2 was due to the recognition of a sialylated O-linked glycan with HEG1 peptide. We also found that gene silencing of HEG1 significantly suppressed the survival and proliferation of mesothelioma cells; this result suggests that HEG1 may be a worthwhile target for function-inhibition drugs. Taken together, our results indicate that sialylated HEG1 may be useful as a diagnostic and therapeutic target for MM.
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spelling pubmed-53747112017-04-03 HEG1 is a novel mucin-like membrane protein that serves as a diagnostic and therapeutic target for malignant mesothelioma Tsuji, Shoutaro Washimi, Kota Kageyama, Taihei Yamashita, Makiko Yoshihara, Mitsuyo Matsuura, Rieko Yokose, Tomoyuki Kameda, Yoichi Hayashi, Hiroyuki Morohoshi, Takao Tsuura, Yukio Yusa, Toshikazu Sato, Takashi Togayachi, Akira Narimatsu, Hisashi Nagasaki, Toshinori Nakamoto, Kotaro Moriwaki, Yasuhiro Misawa, Hidemi Hiroshima, Kenzo Miyagi, Yohei Imai, Kohzoh Sci Rep Article The absence of highly specific markers for malignant mesothelioma (MM) has served an obstacle for its diagnosis and development of molecular-targeting therapy against MM. Here, we show that a novel mucin-like membrane protein, sialylated protein HEG homolog 1 (HEG1), is a highly specific marker for MM. A monoclonal antibody against sialylated HEG1, SKM9-2, can detect even sarcomatoid and desmoplastic MM. The specificity and sensitivity of SKM9-2 to MM reached 99% and 92%, respectively; this antibody did not react with normal tissues. This accurate discrimination by SKM9-2 was due to the recognition of a sialylated O-linked glycan with HEG1 peptide. We also found that gene silencing of HEG1 significantly suppressed the survival and proliferation of mesothelioma cells; this result suggests that HEG1 may be a worthwhile target for function-inhibition drugs. Taken together, our results indicate that sialylated HEG1 may be useful as a diagnostic and therapeutic target for MM. Nature Publishing Group 2017-03-31 /pmc/articles/PMC5374711/ /pubmed/28361969 http://dx.doi.org/10.1038/srep45768 Text en Copyright © 2017, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Tsuji, Shoutaro
Washimi, Kota
Kageyama, Taihei
Yamashita, Makiko
Yoshihara, Mitsuyo
Matsuura, Rieko
Yokose, Tomoyuki
Kameda, Yoichi
Hayashi, Hiroyuki
Morohoshi, Takao
Tsuura, Yukio
Yusa, Toshikazu
Sato, Takashi
Togayachi, Akira
Narimatsu, Hisashi
Nagasaki, Toshinori
Nakamoto, Kotaro
Moriwaki, Yasuhiro
Misawa, Hidemi
Hiroshima, Kenzo
Miyagi, Yohei
Imai, Kohzoh
HEG1 is a novel mucin-like membrane protein that serves as a diagnostic and therapeutic target for malignant mesothelioma
title HEG1 is a novel mucin-like membrane protein that serves as a diagnostic and therapeutic target for malignant mesothelioma
title_full HEG1 is a novel mucin-like membrane protein that serves as a diagnostic and therapeutic target for malignant mesothelioma
title_fullStr HEG1 is a novel mucin-like membrane protein that serves as a diagnostic and therapeutic target for malignant mesothelioma
title_full_unstemmed HEG1 is a novel mucin-like membrane protein that serves as a diagnostic and therapeutic target for malignant mesothelioma
title_short HEG1 is a novel mucin-like membrane protein that serves as a diagnostic and therapeutic target for malignant mesothelioma
title_sort heg1 is a novel mucin-like membrane protein that serves as a diagnostic and therapeutic target for malignant mesothelioma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5374711/
https://www.ncbi.nlm.nih.gov/pubmed/28361969
http://dx.doi.org/10.1038/srep45768
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