Mannose antibody levels in gastric cancer patients (literature review and clinical and experimental study)
https://doi.org/10.17650/1726-9784-2023-22-3-19-27
Abstract
Introduction. Glycans play an important role in the pathogenesis of malignant neoplasms, including stomach cancer. In recent years, the attention of many researchers has been drawn to mannose (Man) – hexose, which is an indispensable component of all N-chains of glycoproteins involved in both normal physiological and pathological processes.
Aim. To investigate the role of innate immunity factors and ways to influence them through mannose and mannose-containing glycans in gastric cancer patients.
Materials and methods. Data on the role of mannose – one of the key monosaccharides in the formation of glycoprotein N-chains – and its binding receptors (mannose receptor, mannose-binding lectin, antibodies) in gastric cancer since 2006 are presented. Levels of anti-glycan antibodies in blood serum samples of 235 gastric cancer patients and 76 healthy donors were evaluated using a glycochip.
Results. It has been shown that the level of IgM-class antibodies to Manβ – the core part of N-glycans – in gastric cancer patients is significantly lower compared to the donor group, regardless of age (p = 0.0001). To assess the effect of age on the levels of antiglycan antibodies, patients were divided into two subgroups – before and after 45 years. In the group under 45 years of age, significant differences in the levels of antiglycan antibodies to Manβ persisted, while significant differences in the levels of antiglycan antibodies to Manβ1-4GlcNAcβ were not observed. when comparing groups of patients and donors older than 45 years, the levels of antibodies to Manβ and Manβ1-4GlcNAcβ were significantly higher only in donors.
Conclusion. Deficiency of humoral immunity may be one of the key factors in the initiation and progression of carcinogenesis in humans. In our work, in patients with stomach cancer, we revealed a deficiency of antiglycan antibodies to Manβ and to Manβ1-4GlcNAcβ – core fragments of N-chains of glycoproteins, and the deficiency increased with age. The results of the study are a promising platform for further research aimed not only at studying the role of anti-mannose antibodies, but also at developing approaches to adoptive immunoprophylaxis.
About the Authors
M. P. NikulinRussian Federation
24 Kashirskoe Shosse, Moscow 115522
N. V. Shilova
Russian Federation
16 / 10 Miklukho-Maclay St., Moscow 117997
A. D. Lipatnikov
Russian Federation
16 / 10 Miklukho-Maclay St., Moscow 117997
A. V. Semyanikhina
Russian Federation
24 Kashirskoe Shosse, Moscow 115522
I. S. Stilidi
Russian Federation
24 Kashirskoe Shosse, Moscow 115522
N. V. Bovin
Russian Federation
16 / 10 Miklukho-Maclay St., Moscow 117997
N. N. Tupitsyn
Russian Federation
24 Kashirskoe Shosse, Moscow 115522
References
1. Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 countries. Доступно по: https://gco.iarc.fr/
2. Ferreira J., Magalhães A., Gomes J. et al. Protein glycosylation in gastric and colorectal cancers: Toward cancer detection and targeted therapeutics. Cancer Lett 2017;387:32–45. DOI: 10.1016/j.canlet.2016.01.044
3. Hakomori S., Kannagi R. Glycosphingolipids as tumorassociated and differentiation markers. J Natl Cancer Inst 1983;71(2):231–51.
4. Kannagi R., Yin J., Miyazaki K. et al. Current relevance of incomplete synthesis and neo-synthesis for cancer-associated alteration of carbohydrate determinants – Hakomori’s concepts revisited. Biochim Biophys Acta 2008;1780(3):525–31. DOI: 10.1016/j.bbagen.2007.10.007
5. Pinho S.S., Reis C.A. Glycosylation in cancer: mechanisms and clinical implications. Nat Rev Cancer 2015;15(9):540–55. DOI: 10.1038/nrc3982
6. Engering A., Cella M., Fluitsma D. et al. Mannose receptor mediated antigen uptake and presentation in human dendritic cells. Adv Exp Med Biol 1997;417:183–7. DOI: 10.1007/978-1-4757-9966-8_31
7. Scorza M., Liguori R., Elce A. et al. Biological role of mannose binding lectin: From newborns to centenarians. Clin Chim Acta 2015;451(Pt A):78–81. DOI: 10.1016/j.cca.2015.03.007
8. Gonzalez P.S., O’Prey J., Cardaci S. et al. Mannose impairs tumour growth and enhances chemotherapy. Nature 2018;563(7733):719–23. DOI: 10.1038/s41586-018-0729-3
9. Gu J., Liang D., Pierzynski J.A. et al. D-mannose: a novel prognostic biomarker for patients with esophageal adenocarcinoma. Carcinogenesis 2017;38(2):162–7. DOI: 10.1093/carcin/bgw207
10. Sanchez-Espiridion B., Liang D., Ajani J.A. et al. Identification of serum markers of esophageal adenocarcinoma by global and targeted metabolic profiling. Clin Gastroenterol Hepatol 2015;13:1730–7. DOI: 10.1016/j.cgh.2015.05.023
11. Ytting H., Christensen I.J., Jensenius J.C. Preoperative mannanbinding lectin pathway and prognosis in colorectal cancer. Cancer Immunol Immunother 2005;54:265–72. DOI: 10.1007/s00262-004-0594-9
12. Sha J., Cao D., Cui R. et al. Mannose Impairs Lung Adenocarcinoma Growth and Enhances the Sensitivity of A549 Cells to Carboplatin. Cancer Manag Res 2020;12: 11077–83. DOI: 10.2147/CMAR.S278673
13. Fan Z., Wang Y., Xiang S. et al. Dual-self-recognizing, stimulusresponsive and carrier-free methotrexate-mannose conjugate nanoparticles with highly synergistic chemotherapeutic effects. J Mater Chem B 2020;8(9):1922–34. DOI: 10.1039/d0tb00049c
14. Zhang Q., Cai Y., Li Q.Y. et al. Targeted delivery of a mannoseconjugated BODIPY photosensitizer by nanomicelles for photodynamic breast cancer therapy. Chemistry 2017;23(57):14307–15. DOI: 10.1002/chem.201702935
15. Bouffard E., Mauriello Jimenez C., El Cheikh K. et al. Efficient photodynamic therapy of prostate cancer cells through an improved targeting of the cation-independent mannose 6-phosphate receptor. Int J Mol Sci 2019;20(11):2809. DOI: 10.3390/ijms20112809
16. Sheikh H., Yarwood H., Ashworth A. et al. Endo180, an endocytic recycling glycoprotein related to the macrophage mannose receptor is expressed on fibroblasts, endothelial cells and macrophages and functions as a lectin receptor. J Cell Sci 2000;113(Pt 6):1021–32. DOI: 10.1242/jcs.113.6.1021
17. Martinez-Pomares L. The mannose receptor. J Leukoc Biol 2012;92(6):1177–86. DOI: 10.1189/jlb.0512231
18. Liu D.R., Guan Q.L., Gao M.T. et al. Mannose receptor as a potential biomarker for gastric cancer: a pilot study. Int J Biol Markers 2017;32(3):278–83. DOI: 10.5301/jbm.5000244
19. Liu S.S., Gao Y., Yin S.P. et al. Expression of Narcissus pseudonarcissus lectin and mannose receptor positive macrophages predict progression and prognosis of patients with gastric cancer. Transl Cancer Res 2020;9(10):5979–93. DOI: 10.21037/tcr-20-1459
20. Ding D., Song Y., Yao Y. et al. Preoperative serum macrophage activated biomarkers soluble mannose receptor (sMR) and soluble haemoglobin scavenger receptor (sCD163), as novel markers for the diagnosis and prognosis of gastric cancer. Oncol Lett 2017;14(3):2982–90. DOI: 10.3892/ol.2017.6547
21. Ding D., Yao Y., Yang C. et al. Identification of mannose receptor and CD163 as novel biomarkers for colorectal cancer. Cancer Biomark 2018;21(3):689–700. DOI: 10.3233/CBM-170796
22. Zhang H., Wang X., Shen Z. et al. Infiltration of diametrically polarized macrophages predicts overall survival of patients with gastric cancer after surgical resection. Gastric Cancer 2015;18(4):740–50. DOI: 10.1007/s10120-014-0422-7
23. Räihä M.R., Puolakkainen P.A. Tumor-associated macrophages (TAMs) as biomarkers for gastric cancer: A review. Chronic Dis Transl Med 2018;4(3):156–63. DOI: 10.1016/j.cdtm.2018.07.001
24. Dommett R.M., Klein N., Turner M.W. Mannose-binding lectin in innate immunity: past, present and future. Tissue Antigens 2006;68(3):193–209. DOI: 10.1111/j.1399-0039.2006.00649.x
25. Turner M.W. Mannose-binding lectin: the pluripotent molecule of the innate immune system. Immunol Today 1996;17(11):532–40. DOI: 10.1016/0167-5699(96)10062-1
26. Baccarelli A., Hou L., Chen J. et al. Mannose-binding lectin-2 genetic variation and stomach cancer risk. Int J Cancer 2006;119:1970–5. DOI: 10.1002/ijc.22075
27. Wang F.Y., Tahara T., Arisawa T. et al. Mannan-binding lectin (MBL) polymorphism and gastric cancer risk in Japanese population. Dig Dis Sci 2008;53(11):2904–8. DOI: 10.1007/s10620-008-0249-3
28. Xie Z., Wang B., Chai Y. et al. Estimation of associations between 10 common gene polymorphisms and gastric cancer: evidence from a meta-analysis. J Clin Pathol 2020;73(6):318–21. DOI: 10.1136/jclinpath-2019-206189
29. Huflejt M.E., Vuskovic M., Vasiliu D. et al. Anti-carbohydrate antibodies of normal sera: findings, surprises and challenges. Mol Immunol 2009;46(15):3037–49. DOI: 10.1016/j.molimm.2009.06.010
30. Smorodin E.P., Sergeyev B.L., Kurtenkov O.A. The characterization of IgG antibodies to GalNAc betaterminated glycans of gastric cancer survivors. Exp Oncol 2014;36(1):38–43. PMID: 24691283
31. Shilova N., Nikulin M., Navakovskiy M. et al. Antibodies to αMAN in gastric cancer. Hæmatopoïesis Immunology 2021;19(1):30–6.
32. Blixt O., Head S., Mondala T. et al. Printed covalent glycan array for ligand profiling of diverse glycan binding proteins. Proc Natl Acad Sci USA 2004;101(49):17033–8. DOI: 0.1073/pnas.0407902101
33. Tupitsyn N. Immunological concept of cancer prevention. Hæmatopoïesis Immunology 2019;17(2):14–32.
Review
For citations:
Nikulin M.P., Shilova N.V., Lipatnikov A.D., Semyanikhina A.V., Stilidi I.S., Bovin N.V., Tupitsyn N.N. Mannose antibody levels in gastric cancer patients (literature review and clinical and experimental study). Russian Journal of Biotherapy. 2023;22(3):19-27. (In Russ.) https://doi.org/10.17650/1726-9784-2023-22-3-19-27