Glycoproteins in the Sera of Oncological Patients
Authors:
L. Hernychová; L. Uhrík; R. Nenutil; M. V. Novotný
Authors‘ workplace:
Regionální centrum aplikované molekulární onkologie, Masarykův onkologický ústav, Brno
Published in:
Klin Onkol 2019; 32(Supplementum 3): 39-45
Category:
Review
doi:
https://doi.org/10.14735/amko20193S
Overview
Background: Glycosylation is a posttranslational modification that is involved in many biological processes and significantly affects the processes associated with tumour progression. Changes in glycan structures on the surface of tumour cells caused by altering levels of glycosyltransferase and glycosidase expression affect proliferation, adhesion, migration and cellular signalling. The presence of aberrant glycan structures and glycoconjugates in the sera of oncological patients has been reported in many cancers. Consequently, many glycoproteins have been approved by the U.S. Food and Drug Administration as tumour biomarkers for clinical investigations. At present, attention is focused on the search for new glycomarkers that are decorated by aberrant glycosylation or are overexpressed in the serum or exosomes due to their active secretion or release from tumour cells to the extracellular space.
Purpose: The aim of this article has been to review the structure of glycans, glycoproteins and other glycoconjugates and to give more details about their functions in the development and progression of tumours. Another aim was to familiarise the reader with selected clinically approved glycoproteins used to diagnose oncological diseases (AFP, PSA, CA 125, HE4). Attention was paid to changes in the glycan structure of these proteins, their function, serum concentrations and clinical use in the diagnostics of cancer.
Keywords:
tumour – glycoproteins – serum – biomarkers
Sources
ST et al. Comprehensive analytical approach toward glycomic characterization and profiling in urinary exosomes. Anal Chem 2017; 89(10): 5364– 5372. doi: 10.1021/ acs.analchem.7b00062.
10. Pinho SS, Reis CA. Glycosylation in cancer: mechanisms and clinical implications. Nat Rev Cancer 2015; 15(9): 540– 555. doi: 10.1038/ nrc3982.
11. Kailemia MJ, Park D, Lebrilla CB. Glycans and glycoproteins as specific biomarkers for cancer. Anal Bioanal Chem 2017; 409(2): 395– 410. doi: 10.1007/ s00216-016-9880-6.
12. Ashkani J, Naidoo KJ. Glycosyltransferase gene expression profiles classify cancer types and propose prognostic subtypes. Sci Rep 2016; 20(6): 26451. doi: 10.1038/ srep26451.
13. Zhang L, Yu D. Exosomes in cancer development, metastasis, and immunity. Biochim Biophys Acta Rev Cancer 2019; 1871(2): 455– 468. doi: 10.1016/ j.bbcan.2019.04.004.
14. Li I, Nabet BY. Exosomes in the tumor microenvironment as mediators of cancer therapy resistance. Mol Cancer 2019; 18(1): 32. doi: 10.1186/ s12943-019-0975-5.
15. Wu H, Chen X, Ji J et al. Progress of exosomes in the diagnosis and treatment of pancreatic cancer. Genet Test Mol Biomarkers 2019; 23(3): 215– 222. doi: 10.1089/ gtmb.2018.0235.
16. Zhang W, Ou X, Wu X. Proteomics profiling of plasma exosomes in epithelial ovarian cancer: a potential role in the coagulation cascade, diagnosis and prognosis. Int J Oncol 2019; 54(5): 1719– 1733. doi: 10.3892/ ijo.2019.4742.
17. Dube DH, Bertozzi CR. Glycans in cancer and inflammation – potential for therapeutics and diagnostics. Nat Rev Drug Discov 2005; 4(6): 477– 488. doi: 10.1038/ nrd1751.
18. Mann BF, Goetz JA, House MG et al. Glycomic and proteomic profiling of pancreatic cyst fluids identifies hyperfucosylated lactosamines on the N-linked glycans of overexpressed glycoproteins. Mol Cell Proteomics 2012; 11(7): M111.015792. doi: 10.1074/ mcp.M111.015792.
19. Lu J, Gu J. Significance of β-galactoside α2,6 sialyltranferase 1 in cancers. Molecules 2015; 20(5): 7509– 7527. doi: 10.3390/ molecules20057509.
20. Cummings RD, Trowbridge IS, Kornfeld S. A mouse lymphoma cell line resistant to the leukoagglutinating lectin from Phaseolus vulgaris is deficient in UDP-GlcNAc: alpha-Dmannoside beta 1,6 N-acetylglucosaminyltransferase. J Biol Chem 1982; 257(22): 13421−13427.
21. Zhao Y, Sato Y, Isaji T et al. Branched N-glycans regulate the biological functions of integrins and cadherins. FEBS J 2008; 275(9): 1939−1948. doi: 10.1111/ j.1742-4658.2008.06346.x.
22. Demetriou M, Nabi IR, Coppolino M et al. Reduced contact-inhibition and substratum adhesion in epithelial cells expressing GlcNAc-transferase V. J Cell Biol 1995; 130(2): 383−392. doi: 10.1083/ jcb.130.2.383.
23. Yamamoto H, Swoger J, Greene S et al. Beta1,6-Nacetylglucosamine-bearing N-glycans in human gliomas: implications for a role in regulating invasivity. Cancer Res 2000; 60(1): 134−142.
24. Yamamoto H, Oviedo A, Sweeley C et al. Alpha2,6-sialylation of cell-surface N-glycans inhibits glioma formation in vivo. Cancer Res 2001; 61(18): 6822−6829.
25. Ito Y, Miyauchi A, Yoshida H et al. Expression of alpha1,6-fucosyltransferase (FUT8) in papillary carcinoma of the thyroid: its linkage to biological aggressiveness and anaplastic transformation. Cancer Lett 2003; 200(2): 167−172. doi: 10.1016/ s0304-3835(03)00383-5.
26. Shinkawa T, Nakamura K, Yamane N et al. The absence of fucose but not the presence of galactose or bisecting N-acetylglucosamine of human IgG1 complex-type oligosaccharides shows the critical role of enhancing antibody-dependent cellular cytotoxicity. J Biol Chem 2003; 278(5): 3466−3473. doi: 10.1074/ jbc.M210665200.
27. Valík D, Nekulová M, Zdražilová Dubská L et al. Doporučení k využití nádorových markerů v klinické praxi. Klin Biochem Metab 2014; 22(43): 22– 39.
28. Bergstrand CG and Czar B. Demonstration of a new protein fraction in serum from the human fetus. Scand J Clin Lab Invest 1956; 8(2): 174. doi: 10.3109/ 00365515609049266.
29. Kirwan A, Utratna M, O’Dwyer ME, et al. Glycosylation-based serum biomarkers for cancer diagnostics and prognostics. Biomed Res Int 2015; 2015: 490531. doi: 10.1155/ 2015/ 490531.
30. Saito S, Ojima H, Ichikawa H et al. Molecular background of α-fetoprotein in liver cancer cells as revealed by global RNA expression analysis. Cancer Science 2008; 99(12): 2402– 2409. doi: 10.1111/ j.1349-7006.2008.00973.x.
31. Johnson PJ, Poon TCW, Hjelm NM et al. Structures of disease-specific serum alpha-fetoprotein isoforms. Br J Cancer 2000; 83(10): 1330– 1337. doi: 10.1054/ bjoc.2000.1441.
32. Kobayashi M, Kuroiwa T, Suda T et al. Fucosylated fraction of alpha-fetoprotein, L3, as a useful prognostic factor in patients with hepatocellular carcinoma with special reference to low concentrations of serum alpha-fetoprotein. Hepatol Res 2007; 37(11): 914– 922. doi: 10.1111/ j.1872-034X.2007.00147.x.
33. Pešl M, Zámečník L, Soukup V et al. Prostatický specifický antigen a odvozené parametry. In: Urologie pro praxi 2004. [online]. Dostupné z: https:/ / www.urologiepropraxi.cz/ pdfs/ uro/ 2004/ 02/ 05.pdf.
34. Isono T, Tanaka T, Kageyama S et al. Structural diversity of cancer-related and non-cancer-related prostatespecific antigen. Clin Chem 2002; 48(12): 2187– 2194.
35. Kyselova Z, Mechref Y, Al Bataineh MM et al. Alterations in the serum glycome due to metastatic prostate cancer. J Prot Res 2007; 6(5): 1822– 1832. doi: 10.1021/ pr060664t.
36. Peracaula R, Barrabés S, Sarrats A et al. Altered glycosylation in tumours focused to cancer diagnosis. Dis Markers 2008; 25(4– 5): 207– 218. doi: 10.1155/ 2008/ 797629.
37. Leymarie N, Griffin PJ, Jonscher K et al. Interlaboratory study on differential analysis of protein glycosylation by mass spectrometry: the ABRF glycoprotein research multi-institutional study 2012. Mol Cell Proteomics 2013; 12(10): 2935– 2951. doi: 10.1074/ mcp.M113.030643.
38. Bast RC Jr, Feeney M, Lazarus H et al. Reactivity of a monoclonal antibody with human ovarian carcinoma. J Clin Invest 1981; 68(5): 1331– 1337. doi: 10.1172/ jci110380.
39. O’Brien TJ, Beard JB, Underwood LJ et al. The CA 125 gene: an extracellular superstructure dominated by repeat sequences. Tumour Biol 2001; 22(6): 348– 366. doi: 10.1159/ 000050638.
40. Yin BW, Lloyd KO. Molecular cloning of the CA125 ovarian cancer antigen: identification as a new mucin, MUC16. J Biol Chem 2001; 276(29): 27371– 27375. doi: 10.1074/ jbc.M103554200.
41. Rump A, Morikawa Y, Tanaka M et al. Binding of ovarian cancer antigen CA125/ MUC16 to mesothelin mediates cell adhesion. J Biol Chem 2004; 279(10): 9190– 9198. doi: 10.1074/ jbc.M312372200.
42. Hattrup CL, Gendler SJ. Structure and function of the cell surface (tethered) mucins. Annu Rev Physiol 2007; 70: 431– 457. doi: 10.1146/ annurev.physiol.70.113006.100659.
43. Tang Z, Qian M, Ho M. The role of mesothelin in tumor progression and targeted therapy. Anticancer Agents Med Chem 2013; 13(2): 276– 280.
44. Drapkin R, von Horsten HH, Lin Y et al. Human epididymis protein 4 (HE4) is a secreted glycoprotein that is overexpressed by serous and endometrioid ovarian carcinomas. Cancer Res 2005; 65(6): 2162– 2169. doi: 10.1158/ 0008-5472.CAN-04-3924.
45. Moore RG, Brown AK, Miller MC et al. Utility of a novel serum tumour biomarker HE4 in patients with endometrioid adenocarcinoma of the uterus. Gynecol Oncol 2008; 110(2): 196– 201. doi: 10.1016/ j.ygyno.2008.04.002.
46. Escudero JM, Auge JM, Filella X et al. The utility of serum human epididymis protein 4 (HE4) in patients with malignant and nonmalignant diseases: comparison with CA125. Clin Chem 2011; 57(11): 1534– 1544. doi: 10.1373/ clinchem.2010.157073.
47. Moore RG, McMeekin DS, Brown AK et al. A novel multiple marker bioassay utilizing HE4 and CA125 for the prediction of ovarian cancer in patients with a pelvic mass.Gynecol Oncol 2009; 112(1): 40– 46. doi: 10.1016/ j.ygyno.2008.08.031.
48. O’Connor BF, Monaghan D, Cawley J et al. Lectin affinity chromatography (LAC). Methods Mol Biol 2017; 1485: 411– 420. doi: 10.1007/ 978-1-4939-6412-3_23.
49. Wu J, Xie X, Nie S et al. Altered expression of sialylated glycoproteins in ovarian cancer sera using lectin-based ELISA assay and quantitative glycoproteomics analysis. J Proteome Res 2013; 12(7): 3342−3352. doi: 10.1021/ pr400169n.
50. Ito H, Hoshi K, Honda T et al. Lectin-based assay for glycoform-specific detection of α2,6-sialylated transferrin and carcinoembryonic antigen in tissue and body fluid. Molecules 2018; 23(6): 1314. doi: 10.3390/ molecules23061314.
51. Hayashi M, Matsuo K, Tanabe K et al. Comprehensive serum glycopeptide spectra analysis (CSGSA): a potential new tool for early detection of ovarian cancer. Cancers (Basel) 2019; 11(5): 591. doi: 10.3390/ cancers11050591.
52. Qiu F, Chen F, Liu D et al. LC-MS/ MS-based screening of new protein biomarkers for cervical precancerous lesions and cervical cancer Nan Fang Yi Ke Da Xue Xue Bao 2019; 39(1): 13– 22. doi: 10.12122/ j.issn.1673-4254.2019.01.03.
53. Gaunitz S, Nagy G, Pohl NL et al. Recent advances in the analysis of complex glycoproteins. Anal Chem 2017; 89(1): 389– 413. doi: 10.1021/ acs.analchem.6b04343.
54. Reily C, Stewart TJ, Renfrow MB et al. Glycosylation in health and disease. Nat Rev Nephrol 2019; 15(6): 346– 366. doi: 10.1038/ s41581-019-0129-4.
Labels
Paediatric clinical oncology Surgery Clinical oncologyArticle was published in
Clinical Oncology
2019 Issue Supplementum 3
Most read in this issue
- Protein Ubiquitination Research in Oncology
- CRISPR-Cas9 as a Tool in Cancer Therapy
- Uncommon EGFR Mutations in Non-Small Cell Lung Cancer and Their Impact on the Treatment
- Glycosylation as an Important Regulator of Antibody Function