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

Our plain-English summary of HEG1 is a novel mucin-like membrane protein that serves as a diagnostic and therapeutic target for malignant mesothelioma, by S. Tsuji, K. Washimi, T. Kageyama, et al (Scientific Reports, 2017).

The study

• Authors: S. Tsuji, K. Washimi, T. Kageyama, M. Yamashita, M. Yoshihara, R. Matsuura, T. Yokose, Y. Kameda, H. Hayashi, T. Morohoshi, Y. Tsuura, T. Yusa, T. Sato, A. Togayachi, H. Narimatsu, T. Nagasaki, K. Nakamoto, Y. Moriwaki, H. Misawa, K. Hiroshima, Y. Miyagi, K. Imai
• Journal: Scientific Reports
• Published: 2017;7:45768
• Cited by: 56 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

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.

In plain English

This laboratory study from Japan developed a mouse antibody, SKM9-2, by immunizing mice with cells from epithelioid malignant pleural mesothelioma, and tested it as a marker for the disease. The study did not examine asbestos exposure. On tissue samples, the antibody stained 119 of 130 malignant pleural mesotheliomas (92%). Five commonly used markers, tested on 95 of these cases, stained 78% to 87%. The antibody stained 9 of 14 sarcomatoid and 2 of 4 desmoplastic cases, and all 3 malignant peritoneal mesotheliomas tested. It stained only 3 of 310 other tumors (99% specificity) and was not detected in major normal organs. It did stain some reactive, non-cancerous mesothelial cells, including in two of six fibrous pleurisy cases. The authors identified the antibody's target as a sugar-coated (sialylated) form of a membrane protein called HEG1. Reducing HEG1 slowed the growth of two mesothelioma cell lines in the laboratory. It did not slow a kidney cell line or a mesothelioma line with less of the target. The authors concluded that the antibody and HEG1 may be useful diagnostic tools and targets for future mesothelioma treatments.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory study: development of a monoclonal antibody, immunohistochemistry on human tissue samples, biochemical identification of the target protein, and gene-silencing experiments in cell lines
• Who was studied: Tissue from 130 cases of malignant pleural mesothelioma diagnosed at six Japanese hospitals between 1997 and 2016. Also 310 samples of other tumors (24 tumor types) from Kanagawa Cancer Center, normal tissues, six fibrous pleurisy cases, one pneumothorax case, and laboratory cell lines.
• Exposure: Not studied: the article did not examine asbestos or other exposures of the patients whose tissue was tested
• Main results:
  • SKM9-2 stained 119 of 130 malignant pleural mesotheliomas (92%). Other markers were tested on 95 cases: calretinin 76/95 (80%), CK5/6 74/95 (78%), podoplanin 78/95 (82%), WT-1 83/95 (87%) and mesothelin 75/95 (79%).
  • By subtype, SKM9-2 stained 89/91 epithelioid (98%), 19/21 biphasic (90%), 9/14 sarcomatoid (64%) and 2/4 desmoplastic (50%) malignant pleural mesotheliomas. Other markers stained 0 to 50% of sarcomatoid and desmoplastic cases.
  • SKM9-2 also stained mesothelioma cells in pleural effusion (7/8, 88%), malignant peritoneal mesotheliomas (3/3) and single cases of pericardial and tunica vaginalis mesothelioma.
  • Among 310 non-mesothelioma tumors, SKM9-2 stained only 3 (one urothelial carcinoma, one leiomyosarcoma, one epithelioid hemangioendothelioma), giving 99% specificity.
  • SKM9-2 was not detected in major normal organs. It stained a few normal or non-cancerous cells, including some capillary lining cells and reactive mesothelial cells. Reactive mesothelial cells were stained in two of six fibrous pleurisy cases.
  • The antibody's target was identified as HEG1, a large membrane protein carrying sialylated sugar chains.
  • Silencing HEG1 reduced growth of two mesothelioma cell lines, ACC-MESO-4 and NCI-H2452 (p less than 0.01). It did not significantly affect HEK293T or ACC-MESO-1, which had less of the target.
• The authors' conclusion: The authors concluded that the SKM9-2 antibody and HEG1 may be productive diagnostic tools and therapeutic targets for malignant mesothelioma. No treatment was tested.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: HEG1, Malignant Mesothelioma, Monoclonal Antibody, Sarcomatoid, Desmoplastic Mesothelioma, Mesothelioma.

Related studies

• Practical utility of insulin-like growth factor II mRNA-binding protein 3, glucose transporter 1, and epithelial membrane antigen for distinguishing malignant mesotheliomas from benign mesothelial proliferations — S. Chang, M.H. Oh, et al. (2014)
• The distinction of adenocarcinoma from malignant mesothelioma in cell blocks of effusions: the role of routine mucin histochemistry and immunohistochemical assessment of carcinoembryonic antigen, keratin proteins, epithelial membrane antigen, and milk fat globule-derived antigen — E.S. Cibas, J.M. Corson, et al. (1987)
• Membranous HEG1 expression is a useful marker in the differential diagnosis of epithelioid and biphasic malignant mesothelioma versus carcinomas — K. Hiroshima, D. Wu, et al. (2021)
• HEG1, BAP1, and MTAP are useful in cytologic diagnosis of malignant mesothelioma with effusion — K. Hiroshima, D. Wu, et al. (2021)
• The "don't eat me" signal CD47 is a novel diagnostic biomarker and potential therapeutic target for diffuse malignant mesothelioma — C.M. Schürch, S. Forster, et al. (2017)
• Anetumab ravtansine: a novel mesothelin-targeting antibody-drug conjugate cures tumors with heterogeneous target expression favored by bystander effect — S. Golfier, C. Kopitz, et al. (2014)

Browse more research in Scientific Reports, or return to medical research.