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

Shoutaro Tsuji, Kota Washimi, Taihei Kageyama, Makiko Yamashita, Mitsuyo Yoshihara, Rieko Matsuura, Tomoyuki Yokose, Yoichi Kameda, Hiroyuki Hayashi, Takao Morohoshi, Yukio Tsuura, Toshikazu Yusa, Takashi Sato, Akira Togayachi, Hisashi Narimatsu, Toshinori Nagasaki, Kotaro Nakamoto, Yasuhiro Moriwaki, Hidemi Misawa, Kenzo HiroshimaYohei Miyagi, Kohzoh Imai

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18 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number45768
JournalScientific reports
Volume7
DOIs
Publication statusPublished - 2017 Mar 31

ASJC Scopus subject areas

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    Tsuji, S., Washimi, K., Kageyama, T., Yamashita, M., Yoshihara, M., Matsuura, R., Yokose, T., Kameda, Y., Hayashi, H., Morohoshi, T., Tsuura, Y., Yusa, T., Sato, T., Togayachi, A., Narimatsu, H., Nagasaki, T., Nakamoto, K., Moriwaki, Y., Misawa, H., ... Imai, K. (2017). HEG1 is a novel mucin-like membrane protein that serves as a diagnostic and therapeutic target for malignant mesothelioma. Scientific reports, 7, [45768]. https://doi.org/10.1038/srep45768