Molecular basis of antibody binding to mucin glycopeptides in lung cancer
文献类型：期刊论文
| 作者 | Qu, Jin2; Yu, Hongtao1,3; Li, Fenge4,12; Zhang, Chunlei4,11; Trad, Ahmad10; Broks, Cory9; Zhang, Bin8; Gong, Ting7; Guo, Zhi12; Li, Yunsen6 |
| 刊名 | INTERNATIONAL JOURNAL OF ONCOLOGY
 |
| 出版日期 | 2016-02 |
| 卷号 | 48期号:2页码:587-594 |
| ISSN号 | 1019-6439 |
| 关键词 | lung cancer glycoproteome glycopeptidome monoclonal antibody mucin Tn antigen sialyl-Tn antigen cancer biomarkers cancer vaccine immunotherapy immunodiagnosis immunomonitoring |
| DOI | 10.3892/ijo.2015.3302 |
| 文献子类 | Article |
| 英文摘要 | Glycopeptides bearing Tn epitopes are emerging targets for cancer diagnosis and immunotherapy. In this study, we analyzed membrane proteins containing O-glycosylated tandem repeat (TR) sequences in lung cancer patients of different types and stages, using gene microarray data in public domain. The expression of Tn and glycopeptide epitopes on the surface of lung cancer cell lines were studied by monoclonal IgG antibodies 14A, 16A, and B72.3. The binding of mAbs to synthetic glycopeptides were studied by surface plasmon resonance. Nine mucin mRNAs were found to be expressed in lung cancer patients but at similar level to healthy individuals. At protein level, a glycopeptide epitope on cancer cell surface is preferably recognized by mAb 16A, as compared to peptide-alone (14A) or sugar-alone epitopes (B72.3). 14A and 16A favor clustered TR containing more than three TR sequences, with 10-fold lower Kd than two consecutive TR. B72.3 preferrably recognized clustered sialyl-Tn displayed on MUC1 but not other O-glycoproteins, with 100-fold stronger binding when MUC1 is transfected as a sugar carrier, while the total sugar epitopes remain unchanged. These findings indicate that clusters of both TR backbones and sugars are essential for mAb binding to mucin glycopeptides. Three rules of antibody binding to mucin glycopeptides at molecular level are presented here: first, the peptide backbone of a glycopeptide is preferentially recognized by B cells through mutations in complementarity determining regions (CDRs) of B cell receptor, and the sugar-binding specificity is acquired through mutations in frame work of heavy chain; secondly, consecutive tandem repeats (TR) of peptides and glycopeptides are preferentially recognized by B cells, which favor clustered TR containing more than three TR sequences; thirdly, certain sugar-specific B cells recognize and accommodate clustered Tn and sialyl-Tn displayed on the surface of a mucin but not other membrane proteins. |
| WOS关键词 | CELL-MEDIATED CYTOTOXICITY ; MONOCLONAL-ANTIBODIES ; SIALYL-TN ; GENE-EXPRESSION ; PEPTIDE ; VACCINE ; EPITOPE ; ANTIGEN ; ADENOCARCINOMA ; GLYCOPROTEOME |
| 资助项目 | National Natural Science Foundation of China[81570007] ; US NIH[AI079232] ; Shanghai Pulmonary Hospital, Tongji University[00000000] ; PRC's 1000 Plan Recruitment Program for Young Talents[00000000] |
| WOS研究方向 | Oncology |
| 语种 | 英语 |
| 出版者 | SPANDIDOS PUBL LTD |
| WOS记录号 | WOS:000366897500016 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/276172]  |
| 专题 | 药物安全性评价中心 |
| 通讯作者 | Zhou, Dapeng |
| 作者单位 | 1.Shanghai Tech Univ, iHuman Inst, Shanghai 201203, Peoples R China; 2.Tongji Univ, Sch Med, Shanghai Pulm Hosp, Shanghai 200092, Peoples R China; 3.Chinese Acad Sci, Shanghai Inst Mat Med, Key Lab Receptor Res, Shanghai 201203, Peoples R China; 4.Mayo Clin, Jacksonville, FL 32224 USA; 5.Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA; 6.Soochow Univ, Inst Biol & Med Sci, Lab Cellular & Mol Tumor Immunol, Jiangsu Key Lab Infect & Immun, Suzhou 215123, Jiangsu, Peoples R China; 7.Univ Texas MD Anderson Canc Ctr, Dept Epigenet & Mol Carcinogenesis, Smithville, TX 78957 USA; 8.Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA; 9.Calif State Univ Fresno, Dept Chem, Fresno, CA 93740 USA; 10.Univ Kiel, Fac Med, Inst Biochem, D-24105 Kiel, Germany; |
| 推荐引用方式 GB/T 7714 | Qu, Jin,Yu, Hongtao,Li, Fenge,et al. Molecular basis of antibody binding to mucin glycopeptides in lung cancer[J]. INTERNATIONAL JOURNAL OF ONCOLOGY,2016,48(2):587-594. |
| APA | Qu, Jin.,Yu, Hongtao.,Li, Fenge.,Zhang, Chunlei.,Trad, Ahmad.,...&Zhou, Dapeng.(2016).Molecular basis of antibody binding to mucin glycopeptides in lung cancer.INTERNATIONAL JOURNAL OF ONCOLOGY,48(2),587-594. |
| MLA | Qu, Jin,et al."Molecular basis of antibody binding to mucin glycopeptides in lung cancer".INTERNATIONAL JOURNAL OF ONCOLOGY 48.2(2016):587-594. |
入库方式： OAI收割
来源：上海药物研究所
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