Skip to main content
Top
Published in: Journal of Ovarian Research 1/2017

Open Access 01-12-2017 | Research

Naturally occurring anti-glycan antibodies binding to Globo H-expressing cells identify ovarian cancer patients

Authors: Tatiana Pochechueva, Shahidul Alam, Andreas Schötzau, Alexander Chinarev, Nicolai V. Bovin, Neville F. Hacker, Francis Jacob, Viola Heinzelmann-Schwarz

Published in: Journal of Ovarian Research | Issue 1/2017

Login to get access

Abstract

Background

Glycosphingolipids are important compounds of the plasma membrane of mammalian cells and a number of them have been associated with malignant transformation and progression, reinforcing tumour aggressiveness and metastasis. Here we investigated the levels of naturally occurring anti-glycan antibodies to Globo H in blood plasma obtained from high-grade serous ovarian cancer patients (SOC) and women without gynaecological malignancies (control) using suspension glycan array technology employing chemically synthesized glycans as antibody targets.

Results

We found that anti-human Globo H IgG antibodies were able to significantly discriminate SOC from controls (P < 0.05). A combination with the clinically used tumour marker CA125 increased the diagnostic performance (AUC 0.8711). We next compared suspension array with standard flow cytometry in plasma samples and found that the level of anti-Globo H antibodies highly correlated (r = 0.992). The incubation of plasma-derived anti-glycan antibodies with chemically synthesized (presented on fluorescence microspheres) and native Globo H (expressed on Globo H-positive cell lines) revealed strong reactivity of naturally occurring human anti-Globo H antibodies towards its antigen expressed on ovarian cancer cells.

Conclusions

Our data demonstrate that human plasma-derived antibodies to Globo H as well as the presence of the antigen might be considered as therapeutic option in ovarian cancer.
Literature
1.
go back to reference Menard S, Tagliabue E, Canevari S, Fossati G, Colnaghi MI. Generation of monoclonal antibodies reacting with normal and cancer cells of human breast. Cancer Res. 1983;43(3):1295–300.PubMed Menard S, Tagliabue E, Canevari S, Fossati G, Colnaghi MI. Generation of monoclonal antibodies reacting with normal and cancer cells of human breast. Cancer Res. 1983;43(3):1295–300.PubMed
2.
go back to reference Kannagi R, Levery SB, Ishigami F, Hakomori S, Shevinsky LH, Knowles BB, et al. New globoseries glycosphingolipids in human teratocarcinoma reactive with the monoclonal antibody directed to a developmentally regulated antigen, stage-specific embryonic antigen 3. J Biol Chem. 1983;258(14):8934–42.PubMed Kannagi R, Levery SB, Ishigami F, Hakomori S, Shevinsky LH, Knowles BB, et al. New globoseries glycosphingolipids in human teratocarcinoma reactive with the monoclonal antibody directed to a developmentally regulated antigen, stage-specific embryonic antigen 3. J Biol Chem. 1983;258(14):8934–42.PubMed
3.
go back to reference Bremer EG, Levery SB, Sonnino S, Ghidoni R, Canevari S, Kannagi R, et al. Characterization of a glycosphingolipid antigen defined by the monoclonal antibody MBr1 expressed in normal and neoplastic epithelial cells of human mammary gland. J Biol Chem. 1984;259(23):14773–7.PubMed Bremer EG, Levery SB, Sonnino S, Ghidoni R, Canevari S, Kannagi R, et al. Characterization of a glycosphingolipid antigen defined by the monoclonal antibody MBr1 expressed in normal and neoplastic epithelial cells of human mammary gland. J Biol Chem. 1984;259(23):14773–7.PubMed
4.
go back to reference Canevari S, Fossati G, Balsari A, Sonnino S, Colnaghi MI. Immunochemical analysis of the determinant recognized by a monoclonal antibody (MBr1) which specifically binds to human mammary epithelial cells. Cancer Res. 1983;43(3):1301–5.PubMed Canevari S, Fossati G, Balsari A, Sonnino S, Colnaghi MI. Immunochemical analysis of the determinant recognized by a monoclonal antibody (MBr1) which specifically binds to human mammary epithelial cells. Cancer Res. 1983;43(3):1301–5.PubMed
5.
go back to reference Zhang S, Cordon-Cardo C, Zhang HS, Reuter VE, Adluri S, Hamilton WB, et al. Selection of tumor antigens as targets for immune attack using immunohistochemistry: I. Focus on gangliosides. Int J Cancer. 1997;73(1):42–9.CrossRefPubMed Zhang S, Cordon-Cardo C, Zhang HS, Reuter VE, Adluri S, Hamilton WB, et al. Selection of tumor antigens as targets for immune attack using immunohistochemistry: I. Focus on gangliosides. Int J Cancer. 1997;73(1):42–9.CrossRefPubMed
8.
go back to reference Tsai YCHJ, Cheng JY, Lin JJ, Hung JT, Wu YY, Yen KT, Yu AL. A prevalent cancer associated glycan, Globo H ceramide, induces immunosupression by reducing Notch 1 signalling. J Cancer Sci Ther. 2013;5(7):264–70.CrossRef Tsai YCHJ, Cheng JY, Lin JJ, Hung JT, Wu YY, Yen KT, Yu AL. A prevalent cancer associated glycan, Globo H ceramide, induces immunosupression by reducing Notch 1 signalling. J Cancer Sci Ther. 2013;5(7):264–70.CrossRef
9.
go back to reference Slovin SF, Ragupathi G, Fernandez C, Jefferson MP, Diani M, Wilton AS, et al. A bivalent conjugate vaccine in the treatment of biochemically relapsed prostate cancer: a study of glycosylated MUC-2-KLH and Globo H-KLH conjugate vaccines given with the new semi-synthetic saponin immunological adjuvant GPI-0100 OR QS-21. Vaccine. 2005;23(24):3114–22. doi:10.1016/j.vaccine.2005.01.072.CrossRefPubMed Slovin SF, Ragupathi G, Fernandez C, Jefferson MP, Diani M, Wilton AS, et al. A bivalent conjugate vaccine in the treatment of biochemically relapsed prostate cancer: a study of glycosylated MUC-2-KLH and Globo H-KLH conjugate vaccines given with the new semi-synthetic saponin immunological adjuvant GPI-0100 OR QS-21. Vaccine. 2005;23(24):3114–22. doi:10.​1016/​j.​vaccine.​2005.​01.​072.CrossRefPubMed
12.
go back to reference Hirche TO, Stein J, Hirche H, Hausmann J, Wagner TO, Behrens F, et al. Increased levels of anti-glycan antibodies in patients with cystic fibrosis. Eur J Med Res. 2011;16(9):385–90.CrossRefPubMedPubMedCentral Hirche TO, Stein J, Hirche H, Hausmann J, Wagner TO, Behrens F, et al. Increased levels of anti-glycan antibodies in patients with cystic fibrosis. Eur J Med Res. 2011;16(9):385–90.CrossRefPubMedPubMedCentral
13.
go back to reference Rieder F, Lopez R, Franke A, Wolf A, Schleder S, Dirmeier A, et al. Characterization of changes in serum anti-glycan antibodies in Crohn's disease - a longitudinal analysis. PLoS One. 2011;6(5):e18172.CrossRefPubMedPubMedCentral Rieder F, Lopez R, Franke A, Wolf A, Schleder S, Dirmeier A, et al. Characterization of changes in serum anti-glycan antibodies in Crohn's disease - a longitudinal analysis. PLoS One. 2011;6(5):e18172.CrossRefPubMedPubMedCentral
15.
go back to reference Jacob F, Goldstein DR, Bovin NV, Pochechueva T, Spengler M, Caduff R, et al. Serum antiglycan antibody detection of nonmucinous ovarian cancers by using a printed glycan array. Int J Cancer. 2012;130(1):138–46. doi:10.1002/ijc.26002.CrossRefPubMed Jacob F, Goldstein DR, Bovin NV, Pochechueva T, Spengler M, Caduff R, et al. Serum antiglycan antibody detection of nonmucinous ovarian cancers by using a printed glycan array. Int J Cancer. 2012;130(1):138–46. doi:10.​1002/​ijc.​26002.CrossRefPubMed
16.
go back to reference Pochechueva T, Jacob F, Goldstein DR, Huflejt ME, Chinarev A, Caduff R, et al. Comparison of printed glycan array, suspension array and ELISA in the detection of human anti-glycan antibodies. Glycoconj J. 2011;28(8–9):507–17.CrossRefPubMedPubMedCentral Pochechueva T, Jacob F, Goldstein DR, Huflejt ME, Chinarev A, Caduff R, et al. Comparison of printed glycan array, suspension array and ELISA in the detection of human anti-glycan antibodies. Glycoconj J. 2011;28(8–9):507–17.CrossRefPubMedPubMedCentral
17.
go back to reference Pedersen JW, Blixt O, Bennett EP, Tarp MA, Dar I, Mandel U, et al. Seromic profiling of colorectal cancer patients with novel glycopeptide microarray. Int J Cancer. 2011;128(8):1860–71. doi:10.1002/ijc.25778.CrossRefPubMed Pedersen JW, Blixt O, Bennett EP, Tarp MA, Dar I, Mandel U, et al. Seromic profiling of colorectal cancer patients with novel glycopeptide microarray. Int J Cancer. 2011;128(8):1860–71. doi:10.​1002/​ijc.​25778.CrossRefPubMed
18.
go back to reference Wandall HH, Blixt O, Tarp MA, Pedersen JW, Bennett EP, Mandel U, et al. Cancer biomarkers defined by autoantibody signatures to aberrant O-glycopeptide epitopes. Cancer Res. 2010;70(4):1306–13.CrossRefPubMed Wandall HH, Blixt O, Tarp MA, Pedersen JW, Bennett EP, Mandel U, et al. Cancer biomarkers defined by autoantibody signatures to aberrant O-glycopeptide epitopes. Cancer Res. 2010;70(4):1306–13.CrossRefPubMed
19.
go back to reference Huflejt ME, Vuskovic M, Vasiliu D, Xu H, Obukhova P, Shilova N, et al. Anti-carbohydrate antibodies of normal sera: findings, surprises and challenges. Mol Immunol. 2009;46(15):3037–49.CrossRefPubMed Huflejt ME, Vuskovic M, Vasiliu D, Xu H, Obukhova P, Shilova N, et al. Anti-carbohydrate antibodies of normal sera: findings, surprises and challenges. Mol Immunol. 2009;46(15):3037–49.CrossRefPubMed
20.
go back to reference Huang CY, Thayer DA, Chang AY, Best MD, Hoffmann J, Head S, et al. Carbohydrate microarray for profiling the antibodies interacting with Globo H tumor antigen. Proc Natl Acad Sci U S A. 2006;103(1):15–20. doi:10.1073/pnas.0509693102.CrossRefPubMed Huang CY, Thayer DA, Chang AY, Best MD, Hoffmann J, Head S, et al. Carbohydrate microarray for profiling the antibodies interacting with Globo H tumor antigen. Proc Natl Acad Sci U S A. 2006;103(1):15–20. doi:10.​1073/​pnas.​0509693102.CrossRefPubMed
22.
go back to reference Pochechueva T, Chinarev A, Spengler M, Korchagina E, Heinzelmann-Schwarz V, Bovin N, et al. Multiplex suspension array for human anti-carbohydrate antibody profiling. Analyst. 2011;136(3):560–9. doi:10.1039/c0an00758g.CrossRefPubMed Pochechueva T, Chinarev A, Spengler M, Korchagina E, Heinzelmann-Schwarz V, Bovin N, et al. Multiplex suspension array for human anti-carbohydrate antibody profiling. Analyst. 2011;136(3):560–9. doi:10.​1039/​c0an00758g.CrossRefPubMed
24.
go back to reference Chinarev AA, Galanina OE, Bovin NV. Biotinylated multivalent glycoconjugates for surface coating. Methods Mol Biol. 2010;600:67–78.CrossRefPubMed Chinarev AA, Galanina OE, Bovin NV. Biotinylated multivalent glycoconjugates for surface coating. Methods Mol Biol. 2010;600:67–78.CrossRefPubMed
25.
26.
go back to reference Sing T, Sander O, Beerenwinkel N, Lengauer T. ROCR: visualizing classifier performance in R. Bioinformatics. 2005;21(20):3940–1.CrossRefPubMed Sing T, Sander O, Beerenwinkel N, Lengauer T. ROCR: visualizing classifier performance in R. Bioinformatics. 2005;21(20):3940–1.CrossRefPubMed
30.
go back to reference Everest-Dass AV, Briggs MT, Kaur G, Oehler MK, Hoffmann P, Packer NH. N-glycan MALDI Imaging Mass Spectrometry on Formalin-Fixed Paraffin-Embedded Tissue Enables the Delineation of Ovarian Cancer Tissues. Mol Cell Proteomics. 2016;15(9):3003–16. doi:10.1074/mcp.M116.059816.CrossRefPubMed Everest-Dass AV, Briggs MT, Kaur G, Oehler MK, Hoffmann P, Packer NH. N-glycan MALDI Imaging Mass Spectrometry on Formalin-Fixed Paraffin-Embedded Tissue Enables the Delineation of Ovarian Cancer Tissues. Mol Cell Proteomics. 2016;15(9):3003–16. doi:10.​1074/​mcp.​M116.​059816.CrossRefPubMed
31.
Metadata
Title
Naturally occurring anti-glycan antibodies binding to Globo H-expressing cells identify ovarian cancer patients
Authors
Tatiana Pochechueva
Shahidul Alam
Andreas Schötzau
Alexander Chinarev
Nicolai V. Bovin
Neville F. Hacker
Francis Jacob
Viola Heinzelmann-Schwarz
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Journal of Ovarian Research / Issue 1/2017
Electronic ISSN: 1757-2215
DOI
https://doi.org/10.1186/s13048-017-0305-8

Other articles of this Issue 1/2017

Journal of Ovarian Research 1/2017 Go to the issue