Molecular basis of antibody binding to mucin glycopeptides in lung cancer

doi:10.3892/ijo.2015.3302

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	Molecular basis of antibody binding to mucin glycopeptides in lung cancer
	Qu, Jin 1; Yu, Hongtao 2,3; Li, Fenge 4,12; Zhang, Chunlei 5,12; Trad, Ahmad 6; Broks, Cory 7; Zhang, Bin 8; Gong, Ting 9; Guo, Zhi 4; Li, Yunsen 10; Ragupathi, Govind 11; Lou, Yanyan 12; Hwu, Patrick 13; Huang, Wei2,3 ; Zhou, Dapeng 1
	2016-02
发表期刊	INTERNATIONAL JOURNAL OF ONCOLOGY (IF:4.5[JCR-2023],4.6[5-Year])
ISSN	1019-6439
卷号	48 期号:2 页码:587-594
发表状态	已发表
DOI	10.3892/ijo.2015.3302
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.
关键词	lung cancer glycoproteome glycopeptidome monoclonal antibody mucin Tn antigen sialyl-Tn antigen cancer biomarkers cancer vaccine immunotherapy immunodiagnosis immunomonitoring
收录类别	SCI
语种	英语
资助项目	US NIH[AI079232]
WOS研究方向	Oncology
WOS类目	Oncology
WOS记录号	WOS:000366897500016
出版者	SPANDIDOS PUBL LTD
WOS关键词	CELL-MEDIATED CYTOTOXICITY ; MONOCLONAL-ANTIBODIES ; SIALYL-TN ; GENE-EXPRESSION ; PEPTIDE ; VACCINE ; EPITOPE ; ANTIGEN ; ADENOCARCINOMA ; GLYCOPROTEOME
原始文献类型	Article
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/1932
专题	iHuman研究所 iHuman研究所_PI研究组_程建军组
通讯作者	Zhou, Dapeng
作者单位	1.Tongji Univ, Sch Med, Shanghai Pulm Hosp, Shanghai 200092, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, Key Lab Receptor Res, Shanghai 201203, Peoples R China 3.Shanghai Tech Univ, iHuman Inst, Shanghai 201203, Peoples R China 4.Tianjin Canc Hosp, Tianjin 300060, Peoples R China 5.Shenzhen Hosp Chinese Med, Shenzhen 518033, Guangdong, Peoples R China 6.Univ Kiel, Fac Med, Inst Biochem, D-24105 Kiel, Germany 7.Calif State Univ Fresno, Dept Chem, Fresno, CA 93740 USA 8.Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA 9.Univ Texas MD Anderson Canc Ctr, Dept Epigenet & Mol Carcinogenesis, Smithville, TX 78957 USA 10.Soochow Univ, Inst Biol & Med Sci, Lab Cellular & Mol Tumor Immunol, Jiangsu Key Lab Infect & Immun, Suzhou 215123, Jiangsu, Peoples R China 11.Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA 12.Mayo Clin, Jacksonville, FL 32224 USA 13.Univ Texas MD Anderson Canc Ctr, Div Canc Med, Houston, TX 77030 USA
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.