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

• DOI: 10.1038/srep45768
• Publication Date: 2017-03-31T14:34:05Z
• Authors: 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 Hiroshima; Yohei Miyagi; Kohzoh Imai
• Keywords: Mesothelioma; 0301 basic medicine; Glycosylation; Lung Neoplasms; Mesothelioma, Malignant; Antibodies, Monoclonal; Membrane Proteins; Sensitivity and Specificity; Article; 3. Good health; 03 medical and health sciences; 0302 clinical medicine; Cell Line, Tumor; Biomarkers, Tumor; Humans; Cell Proliferation

AbstractThe 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.