title: HEG1 is a novel mucin-like membrane protein that serves as a diagnostic and therapeutic target for malignant mesothelioma.
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.
authors.affiliation: Kanagawa Cancer Center Research Institute, Yokohama, Japan.
authors.forename: Shoutaro
authors.initials: S
authors.lastname: Tsuji
authors.affiliation: Kanagawa Cancer Center Research Institute, Yokohama, Japan.|Department of Pathology, Kanagawa Cancer Center, Yokohama, Japan.
authors.forename: Kota
authors.initials: K
authors.lastname: Washimi
authors.affiliation: Kanagawa Cancer Center Research Institute, Yokohama, Japan.
authors.forename: Taihei
authors.initials: T
authors.lastname: Kageyama
authors.affiliation: Kanagawa Cancer Center Research Institute, Yokohama, Japan.
authors.forename: Makiko
authors.initials: M
authors.lastname: Yamashita
authors.affiliation: Kanagawa Cancer Center Research Institute, Yokohama, Japan.
authors.forename: Mitsuyo
authors.initials: M
authors.lastname: Yoshihara
authors.affiliation: Kanagawa Cancer Center Research Institute, Yokohama, Japan.
authors.forename: Rieko
authors.initials: R
authors.lastname: Matsuura
authors.affiliation: Department of Pathology, Kanagawa Cancer Center, Yokohama, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Yokose
authors.affiliation: Department of Pathology, Kanagawa Cardiovascular and Respiratory Center, Yokohama, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Kameda
authors.affiliation: Department of Pathology, Yokohama Municipal Citizen's Hospital, Yokohama, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Hayashi
authors.affiliation: Division of General Thoracic Surgery, Yokosuka-Kyosai Hospital, Yokosuka, Japan.
authors.forename: Takao
authors.initials: T
authors.lastname: Morohoshi
authors.affiliation: Division of Pathology, Yokosuka-Kyosai Hospital, Yokosuka, Japan.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Tsuura
authors.affiliation: Department of General Thoracic Surgery and Asbestos Disease Center, Chiba Rosai Hospital, Ichihara, Japan.
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Yusa
authors.affiliation: Research Center for Medical Glycoscience, National Institute of Advanced Industrial Science and Technology, Tsukuba, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Sato
authors.affiliation: Research Center for Medical Glycoscience, National Institute of Advanced Industrial Science and Technology, Tsukuba, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Togayachi
authors.affiliation: Research Center for Medical Glycoscience, National Institute of Advanced Industrial Science and Technology, Tsukuba, Japan.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Narimatsu
authors.affiliation: Kanagawa Cancer Center Research Institute, Yokohama, Japan.|Division of Pharmacology, Faculty of Pharmacy, Keio University, Tokyo, Japan.
authors.forename: Toshinori
authors.initials: T
authors.lastname: Nagasaki
authors.affiliation: Kanagawa Cancer Center Research Institute, Yokohama, Japan.|Division of Pharmacology, Faculty of Pharmacy, Keio University, Tokyo, Japan.
authors.forename: Kotaro
authors.initials: K
authors.lastname: Nakamoto
authors.affiliation: Division of Pharmacology, Faculty of Pharmacy, Keio University, Tokyo, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Moriwaki
authors.affiliation: Division of Pharmacology, Faculty of Pharmacy, Keio University, Tokyo, Japan.
authors.forename: Hidemi
authors.initials: H
authors.lastname: Misawa
authors.affiliation: Department of Pathology, Tokyo Women's Medical University, Yachiyo Medical Center, Yachiyo, Japan.
authors.forename: Kenzo
authors.initials: K
authors.lastname: Hiroshima
authors.affiliation: Kanagawa Cancer Center Research Institute, Yokohama, Japan.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Miyagi
authors.affiliation: Kanagawa Cancer Center Research Institute, Yokohama, Japan.|Institute of Medical Science, University of Tokyo, Tokyo, Japan.
authors.forename: Kohzoh
authors.initials: K
authors.lastname: Imai
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000276:immunology / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D006031:Glycosylation; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000276:immunology* / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008654:Mesothelioma / Q000175:diagnosis* / Q000276:immunology* / Q000378:metabolism; D000086002:Mesothelioma, Malignant; D012680:Sensitivity and Specificity
chemical_list: D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor; C584441:HEG1 protein, human; D008565:Membrane Proteins