論文種別 | 原著(症例報告除く) |
言語種別 | 英語 |
査読の有無 | その他(不明) |
表題 | Expression of Heart Development Protein With EGF-Like Domains 1 (HEG1) Decorated With Low-Sulfated Keratan Sulfate in Human Malignant Pleural Mesothelioma. |
掲載誌名 | 正式名:Pathology international 略 称:Pathol Int ISSNコード:14401827/13205463 |
掲載区分 | 国外 |
巻・号・頁 | pp.Online ahead of print |
著者・共著者 | Koki Nakashima, Hitomi Hoshino, Zui Zhang, Tomoya O Akama, Nobuyuki Kondo, Seiki Hasegawa, Yoshitaka Sekido, Mana Fukushima, Tamotsu Ishizuka, Motohiro Kobayashi |
発行年月 | 2025/06 |
概要 | The glycoform of heart development protein with EGF-like domains 1 (HEG1) recognized by the SKM9-2 monoclonal antibody is a useful diagnostic marker for malignant pleural mesothelioma (MPM). The putative glycoform includes core 2 O-glycans carrying sialyl poly-N-acetyllactosamine (LacNAc), but sulfation modifications are undetermined. Since sialyl 6-sulfo LacNAc-capped core 2 O-glycans are expressed in MPM and their structure overlaps with low-sulfated keratan sulfate (KS), we asked whether low-sulfated KS is expressed in MPM and whether HEG1 is decorated with low-sulfated KS. We performed immunohistochemical analysis of 41 MPM cases using anti-KS monoclonal antibodies and endoglycosidases, reversed-phase ion-pair high-performance liquid chromatography analysis of KS/sulfated LacNAc isolated from human pleural tissue, and western blot analysis of HEG1·IgG recombinant fusion proteins secreted from low-sulfated KS-expressing human embryonic kidney cells. Most MPM tissues were stained with anti-low-sulfated KS antibodies and staining was eliminated by endo-β-galactosidase and keratanase II but not by peptide-N-glycosidase F. Disaccharide composition analysis revealed that mono-sulfated LacNAc disaccharide and di-sulfated LacNAc disaccharide accounted for 83.1% and 16.9% of pleural KS/sulfated LacNAc, respectively. Western blot analysis of HEG1·IgG glycoforms indicated that HEG1 functions as a core protein for low-sulfated KS. Thus, HEG1 protein decorated with low-sulfated KS is expressed in MPM. |
DOI | 10.1111/pin.70033 |
PMID | 40525709 |