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	75(10),pp.504-512
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	2025/10
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