| RRC ID |
54133
|
| 著者 |
Matsuura R, Kaji H, Tomioka A, Sato T, Narimatsu H, Moriwaki Y, Misawa H, Imai K, Tsuji S.
|
| タイトル |
Identification of mesothelioma-specific sialylated epitope recognized with monoclonal antibody SKM9-2 in a mucin-like membrane protein HEG1.
|
| ジャーナル |
Sci Rep
|
| Abstract |
The anti-mesothelioma mAb SKM9-2 recognizes the sialylated protein HEG homolog 1 (HEG1). HEG1 is a 400 kDa mucin-like membrane protein found on mesothelioma. SKM9-2 can detect mesothelioma more specifically and sensitively than other antibodies against current mesothelioma markers; therefore, SKM9-2 would be likely useful for the precise detection and diagnosis of malignant mesothelioma. In the present study, we investigated the epitope of SKM9-2. We analyzed the binding of SKM9-2 to truncated HEG1 and candidate epitope-fused glycosylphosphatidylinositol-anchor proteins. The epitope of SKM9-2 was identified as an O-glycosylated region, 893-SKSPSLVSLPT-903, in HEG1. An alanine scanning assay of the epitope showed that SKM9-2 bound to a simple epitope in HEG1, and the SKxPSxVS sequence within the epitope was essential for SKM9-2 recognition. Mass spectrometry analysis and lectin binding analysis of soluble epitope peptides indicated that the SKM9-2 epitope, in which Ser897 was not glycosylated, contained two disialylated core 1 O-linked glycan-modified serine residues, Ser893 and Ser900. Neuraminidase treatment analysis also confirmed that the epitope in mesothelioma cells contained a similar glycan modification. The specific detection of mesothelioma with SKM9-2 can thus be performed by the recognition of sialylated glycan modification in the specific region of HEG1.
|
| 巻・号 |
8(1)
|
| ページ |
14251
|
| 公開日 |
2018-9-24
|
| DOI |
10.1038/s41598-018-32534-8
|
| PII |
10.1038/s41598-018-32534-8
|
| PMID |
30250045
|
| PMC |
PMC6155162
|
| MeSH |
Antibodies, Monoclonal / genetics
Antibodies, Monoclonal / immunology*
Cell Line, Tumor
Enzyme-Linked Immunosorbent Assay
Epitopes / genetics*
Epitopes / immunology
Glycosylation
Humans
Lectins / chemistry
Lectins / immunology
Lung Neoplasms / genetics*
Lung Neoplasms / immunology
Lung Neoplasms / pathology
Mass Spectrometry
Membrane Proteins / genetics*
Membrane Proteins / immunology
Mesothelioma / genetics*
Mesothelioma / immunology
Mesothelioma / pathology
Mesothelioma, Malignant
N-Acetylneuraminic Acid / metabolism
Peptides / genetics
Peptides / immunology
Polysaccharides / genetics
Polysaccharides / metabolism
Protein Binding / genetics
Protein Binding / immunology
|
| IF |
3.998
|
| 引用数 |
2
|
| リソース情報 |
| ヒト・動物細胞 |
ACC-MESO-1(RCB2292)
ACC-MESO-4(RCB2293)
293T(RCB2202) |
