Lung Tumor Cells with Different Tn Antigen Expression Present Distinctive Immunomodulatory Properties
Abstract
:1. Introduction
2. Results and Discussion
2.1. Incomplete O-Glycosylation Alters the Glycophenotype of LL/2 Cells
2.2. MGL2 Differentially Recognizes Tn+ LL/2 Cells
2.3. LL/2-Tn+-H12 and LL/2-Tn+-F9 Differ in Their Ability to Modulate Bone-Marrow-Derived DC (BMDC) Function
3. Materials and Methods
3.1. Mice
3.2. Generation of Tn+ Cells
3.3. SDS-PAGE and Western Blot
3.4. Glycophenotyping of Tumor Cells
3.5. Cell Surface MGL2 Recognition of Tumor Cells
3.6. BMDC Functional Assays
3.7. Statistical Analyses
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Bray, F.; Ferlay, J.; Soerjomataram, I.; Siegel, R.L.; Torre, L.A.; Jemal, A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 2018, 68, 394–424. [Google Scholar] [CrossRef] [Green Version]
- Sung, H.; Ferlay, J.; Siegel, R.L.; Laversanne, M.; Soerjomataram, I.; Jemal, A.; Bray, F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J. Clin. 2021, 71, 209–249. [Google Scholar] [CrossRef] [PubMed]
- da Costa, V.; Freire, T. Advances in the Immunomodulatory Properties of Glycoantigens in Cancer. Cancers 2022, 14, 1854. [Google Scholar] [CrossRef] [PubMed]
- Liang, Y.; Han, P.; Wang, T.; Ren, H.; Gao, L.; Shi, P.; Zhang, S.; Yang, A.; Li, Z.; Chen, M. Stage-associated differences in the serum N- and O-glycan profiles of patients with non-small cell lung cancer. Clin. Proteom. 2019, 16, 20–30. [Google Scholar] [CrossRef]
- Lucchetta, M.; da Piedade, I.; Mounir, M.; Vabistsevits, M.; Terkelsen, T.; Papaleo, E. Distinct signatures of lung cancer types: Aberrant mucin O-glycosylation and compromised immune response. BMC Cancer 2019, 19, 824. [Google Scholar] [CrossRef]
- Fu, C.; Zhao, H.; Wang, Y.; Cai, H.; Xiao, Y.; Zeng, Y.; Chen, H. Tumor-associated antigens: Tn antigen, sTn antigen, and T antigen. HLA 2016, 88, 275–286. [Google Scholar] [CrossRef]
- Liu, Z.; Liu, J.; Dong, X.; Hu, X.; Jiang, Y.; Li, L.; Du, T.; Yang, L.; Wen, T.; An, G.; et al. Tn antigen promotes human colorectal cancer metastasis via H-Ras mediated epithelial-mesenchymal transition activation. J. Cell Mol. Med. 2019, 23, 2083–2092. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ju, T.; Lanneau, G.S.; Gautam, T.; Wang, Y.; Xia, B.; Stowell, S.R.; Willard, M.T.; Wang, W.; Xia, J.Y.; Zuna, R.E.; et al. Human tumor antigens Tn and sialyl Tn arise from mutations in Cosmc. Cancer Res. 2008, 68, 1636–1646. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Yoo, N.J.; Kim, M.S.; Lee, S.H. Absence of COSMC gene mutations in breast and colorectal carcinomas. APMIS 2008, 116, 154–155. [Google Scholar] [CrossRef]
- Raman, J.; Guan, Y.; Perrine, C.L.; Gerken, T.A.; Tabak, L.A. UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosaminyltransferases: Completion of the family tree. Glycobiology 2012, 22, 768–777, Erratum in Glycobiology 2015, 25, 465. https://doi.org/10.1093/glycob/cwv003. [Google Scholar] [CrossRef]
- Li, Z.; Yamada, S.; Inenaga, S.; Imamura, T.; Wu, Y.; Wang, K.Y.; Shimajiri, S.; Nakano, R.; Izumi, H.; Kohno, K.; et al. Polypeptide N-acetylgalactosaminyltransferase 6 expression in pancreatic cancer is an independent prognostic factor indicating better overall survival. Br. J. Cancer 2011, 104, 1882–1889. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Guda, K.; Moinova, H.; He, J.; Jamison, O.; Ravi, L.; Natale, L.; Lutterbaugh, J.; Lawrence, E.; Lewis, S.; Willson, J.K.; et al. Inactivating germ-line and somatic mutations in polypeptide N-acetylgalactosaminyltransferase 12 in human colon cancers. Proc. Natl. Acad. Sci. USA 2009, 106, 12921–12925. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Peng, R.Q.; Wan, H.Y.; Li, H.F.; Liu, M.; Li, X.; Tang, H. MicroRNA-214 suppresses growth and invasiveness of cervical cancer cells by targeting UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase 7. J. Biol. Chem. 2012, 287, 14301–14309. [Google Scholar] [CrossRef] [Green Version]
- Park, J.H.; Nishidate, T.; Kijima, K.; Ohashi, T.; Takegawa, K.; Fujikane, T.; Hirata, K.; Nakamura, Y.; Katagiri, T. Critical roles of mucin 1 glycosylation by transactivated polypeptide N-acetylgalactosaminyltransferase 6 in mammary carcinogenesis. Cancer Res. 2010, 70, 2759–2769. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Haji-Ghassemi, O.; Gilbert, M.; Spence, J.; Schur, M.J.; Parker, M.J.; Jenkins, M.L.; Burke, J.E.; van Faassen, H.; Young, N.M.; Evans, S.V. Molecular Basis for Recognition of the Cancer Glycobiomarker, LacdiNAc (GalNAc[beta1-->4]GlcNAc), by Wisteria floribunda Agglutinin. J. Biol. Chem. 2016, 291, 24085–24095. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Rabinovich, G.A.; Croci, D.O. Regulatory circuits mediated by lectin-glycan interactions in autoimmunity and cancer. Immunity 2012, 36, 322–335. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- McGreal, E.P.; Miller, J.L.; Gordon, S. Ligand recognition by antigen-presenting cell C-type lectin receptors. Curr. Opin. Immunol. 2005, 17, 18–24. [Google Scholar] [CrossRef]
- van Vliet, S.J.; Saeland, E.; van Kooyk, Y. Sweet preferences of MGL: Carbohydrate specificity and function. Trends Immunol. 2008, 29, 83–90. [Google Scholar] [CrossRef]
- Denda-Nagai, K.; Kubota, N.; Tsuiji, M.; Kamata, M.; Irimura, T. Macrophage C-type lectin on bone marrow-derived immature dendritic cells is involved in the internalization of glycosylated antigens. Glycobiology 2002, 12, 443–450. [Google Scholar] [CrossRef] [Green Version]
- Higashi, N.; Fujioka, K.; Denda-Nagai, K.; Hashimoto, S.; Nagai, S.; Sato, T.; Fujita, Y.; Morikawa, A.; Tsuiji, M.; Miyata-Takeuchi, M.; et al. The macrophage C-type lectin specific for galactose/N-acetylgalactosamine is an endocytic receptor expressed on monocyte-derived immature dendritic cells. J. Biol. Chem. 2002, 277, 20686–20693. [Google Scholar] [CrossRef]
- van Vliet, S.J.; van Liempt, E.; Geijtenbeek, T.B.; van Kooyk, Y. Differential regulation of C-type lectin expression on tolerogenic dendritic cell subsets. Immunobiology 2006, 211, 577–585. [Google Scholar] [CrossRef]
- van Vliet, S.J.; Gringhuis, S.I.; Geijtenbeek, T.B.; van Kooyk, Y. Regulation of effector T cells by antigen-presenting cells via interaction of the C-type lectin MGL with CD45. Nat. Immunol. 2006, 7, 1200–1208. [Google Scholar] [CrossRef] [PubMed]
- van Vliet, S.J.; Bay, S.; Vuist, I.M.; Kalay, H.; Garcia-Vallejo, J.J.; Leclerc, C.; van Kooyk, Y. MGL signaling augments TLR2-mediated responses for enhanced IL-10 and TNF-alpha secretion. J. Leukoc. Biol. 2013, 94, 315–323. [Google Scholar] [CrossRef] [PubMed]
- Zhang, X.; Jin, X.; Sun, R.; Zhang, M.; Lu, W.; Zhao, M. Gene knockout in cellular immunotherapy: Application and limitations. Cancer. Lett. 2022, 540, 215736. [Google Scholar] [CrossRef] [PubMed]
- Gonzalez-Salinas, F.; Martinez-Amador, C.; Trevino, V. Characterizing genes associated with cancer using the CRISPR/Cas9 system: A systematic review of genes and methodological approaches. Gene 2022, 833, 146595. [Google Scholar] [CrossRef]
- Yu, X.; Du, Z.; Sun, X.; Shi, C.; Zhang, H.; Hu, T. Aberrant Cosmc genes result in Tn antigen expression in human colorectal carcinoma cell line HT-29. Int. J. Clin. Exp. Pathol. 2015, 8, 2590–2602. [Google Scholar]
- Ju, T.; Aryal, R.P.; Kudelka, M.R.; Wang, Y.; Cummings, R.D. The Cosmc connection to the Tn antigen in cancer. Cancer Biomark. 2014, 14, 63–81. [Google Scholar] [CrossRef] [Green Version]
- Cornelissen, L.A.M.; Blanas, A.; Zaal, A.; van der Horst, J.C.; Kruijssen, L.J.W.; O’Toole, T.; van Kooyk, Y.; van Vliet, S.J. Tn antigen expression contributes to an immune suppressive microenvironment and drives tumor growth in colorectal cancer. Front. Oncology 2020, 10, 1622. [Google Scholar] [CrossRef]
- da Costa, V.; van Vliet, S.J.; Carasi, P.; Frigerio, S.; Garcia, P.A.; Croci, D.O.; Festari, M.F.; Costa, M.; Landeira, M.; Rodriguez-Zraquia, S.A.; et al. The Tn antigen promotes lung tumor growth by fostering immunosuppression and angiogenesis via interaction with Macrophage Galactose-type lectin 2 (MGL2). Cancer Lett. 2021, 518, 72–81. [Google Scholar] [CrossRef]
- Festari, M.F.; da Costa, V.; Rodriguez-Zraquia, S.A.; Costa, M.; Landeira, M.; Lores, P.; Solari-Saquieres, P.; Kramer, M.G.; Freire, T. The tumour-associated Tn antigen fosters lung metastasis and recruitment of regulatory T cells in triple negative breast cancer. Glycobiology 2021, 32, 366–379. [Google Scholar] [CrossRef]
- Dusoswa, S.A.; Verhoeff, J.; Abels, E.; Mendez-Huergo, S.P.; Croci, D.O.; Kuijper, L.H.; de Miguel, E.; Wouters, V.; Best, M.G.; Rodriguez, E.; et al. Glioblastomas exploit truncated O-linked glycans for local and distant immune modulation via the macrophage galactose-type lectin. Proc. Natl. Acad. Sci. USA 2020, 117, 3693–3703. [Google Scholar] [CrossRef] [PubMed]
- Osinaga, E.; Bay, S.; Tello, D.; Babino, A.; Pritsch, O.; Assemat, K.; Cantacuzene, D.; Nakada, H.; Alzari, P. Analysis of the fine specificity of Tn-binding proteins using synthetic glycopeptide epitopes and a biosensor based on surface plasmon resonance spectroscopy. FEBS Lett. 2000, 469, 24–28. [Google Scholar] [CrossRef] [Green Version]
- Tachibana, K.; Nakamura, S.; Wang, H.; Iwasaki, H.; Tachibana, K.; Maebara, K.; Cheng, L.; Hirabayashi, J.; Narimatsu, H. Elucidation of binding specificity of Jacalin toward O-glycosylated peptides: Quantitative analysis by frontal affinity chromatography. Glycobiology 2006, 16, 46–53. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hammarstrom, S.; Murphy, L.A.; Goldstein, I.J.; Etzler, M.E. Carbohydrate binding specificity of four N-acetyl-D-galactosamine- “specific” lectins: Helix pomatia A hemagglutinin, soy bean agglutinin, lima bean lectin, and Dolichos biflorus lectin. Biochemistry 1977, 16, 2750–2755. [Google Scholar] [CrossRef]
- Sagar, S.; Leiphrakpam, P.D.; Thomas, D.; McAndrews, K.L.; Caffrey, T.C.; Swanson, B.J.; Clausen, H.; Wandall, H.H.; Hollingsworth, M.A.; Radhakrishnan, P. MUC4 enhances gemcitabine resistance and malignant behaviour in pancreatic cancer cells expressing cancer-associated short O-glycans. Cancer Lett. 2021, 503, 91–102. [Google Scholar] [CrossRef]
- Sheta, R.; Bachvarova, M.; Macdonald, E.; Gobeil, S.; Vanderhyden, B.; Bachvarov, D. The polypeptide GALNT6 Displays Redundant Functions upon Suppression of its Closest Homolog GALNT3 in Mediating Aberrant O-Glycosylation, Associated with Ovarian Cancer Progression. Int. J. Mol. Sci. 2019, 20, 2264. [Google Scholar] [CrossRef] [Green Version]
- Freitas, D.; Campos, D.; Gomes, J.; Pinto, F.; Macedo, J.A.; Matos, R.; Mereiter, S.; Pinto, M.T.; Polonia, A.; Gartner, F.; et al. O-glycans truncation modulates gastric cancer cell signaling and transcription leading to a more aggressive phenotype. EBioMedicine 2019, 40, 349–362. [Google Scholar] [CrossRef] [Green Version]
- Mazal, D.; Lo-Man, R.; Bay, S.; Pritsch, O.; Deriaud, E.; Ganneau, C.; Medeiros, A.; Ubillos, L.; Obal, G.; Berois, N.; et al. Monoclonal antibodies toward different Tn-amino acid backbones display distinct recognition patterns on human cancer cells. Implications for effective immuno-targeting of cancer. Cancer Immunol. Immunother. 2013, 62, 1107–1122. [Google Scholar] [CrossRef]
- Marcelo, F.; Supekar, N.; Corzana, F.; van der Horst, J.C.; Vuist, I.M.; Live, D.; Boons, G.P.H.; Smith, D.F.; van Vliet, S.J. Identification of a secondary binding site in human macrophage galactose-type lectin by microarray studies: Implications for the molecular recognition of its ligands. J. Biol. Chem. 2019, 294, 1300–1311. [Google Scholar] [CrossRef] [Green Version]
- Kumamoto, Y.; Linehan, M.; Weinstein, J.S.; Laidlaw, B.J.; Craft, J.E.; Iwasaki, A. CD301b(+) dermal dendritic cells drive T helper 2 cell-mediated immunity. Immunity 2013, 39, 733–743. [Google Scholar] [CrossRef] [Green Version]
- Freire, T.; Zhang, X.; Deriaud, E.; Ganneau, C.; Vichier-Guerre, S.; Azria, E.; Launay, O.; Lo-Man, R.; Bay, S.; Leclerc, C. Glycosidic Tn-based vaccines targeting dermal dendritic cells favor germinal center B-cell development and potent antibody response in the absence of adjuvant. Blood 2010, 116, 3526–3536. [Google Scholar] [CrossRef] [PubMed]
- Li, D.; Romain, G.; Flamar, A.L.; Duluc, D.; Dullaers, M.; Li, X.H.; Zurawski, S.; Bosquet, N.; Palucka, A.K.; Le Grand, R.; et al. Targeting self- and foreign antigens to dendritic cells via DC-ASGPR generates IL-10-producing suppressive CD4+ T cells. J. Exp. Med. 2012, 209, 109–121. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Karin, M. Nuclear factor-kappaB in cancer development and progression. Nature 2006, 441, 431–436. [Google Scholar] [CrossRef] [PubMed]
- Wesch, D.; Peters, C.; Siegers, G.M. Human gamma delta T regulatory cells in cancer: Fact or fiction? Front. Immunol. 2014, 5, 598. [Google Scholar] [CrossRef] [Green Version]
- Jurisic, V. Multiomic analysis of cytokines in immuno-oncology. Expert. Rev. Proteomics 2020, 17, 663–674. [Google Scholar] [CrossRef]
- Konjevic, G.M.; Vuletic, A.M.; Mirjacic Martinovic, K.M.; Larsen, A.K.; Jurisic, V.B. The role of cytokines in the regulation of NK cells in the tumor environment. Cytokine 2019, 117, 30–40. [Google Scholar] [CrossRef]
- Jurisic, V.; Srdic-Rajic, T.; Konjevic, G.; Bogdanovic, G.; Colic, M. TNF-alpha induced apoptosis is accompanied with rapid CD30 and slower CD45 shedding from K-562 cells. J. Membr. Biol. 2011, 239, 115–122. [Google Scholar] [CrossRef]
- Freire, T.; Lo-Man, R.; Bay, S.; Leclerc, C. Tn glycosylation of the MUC6 protein modulates its immunogenicity and promotes the induction of Th17-biased T cell responses. J. Biol. Chem. 2011, 286, 7797–7811. [Google Scholar] [CrossRef] [Green Version]
- Ju, T.; Xia, B.; Aryal, R.P.; Wang, W.; Wang, Y.; Ding, X.; Mi, R.; He, M.; Cummings, R.D. A novel fluorescent assay for T-synthase activity. Glycobiology 2011, 21, 352–362. [Google Scholar] [CrossRef] [Green Version]
- van Vliet, S.J.; Aarnoudse, C.A.; Broks-van den Berg, V.C.; Boks, M.; Geijtenbeek, T.B.; van Kooyk, Y. MGL-mediated internalization and antigen presentation by dendritic cells: A role for tyrosine-5. Eur. J. Immunol. 2007, 37, 2075–2081. [Google Scholar] [CrossRef]
- Puri, K.D.; Gopalakrishnan, B.; Surolia, A. Carbohydrate binding specificity of the Tn-antigen binding lectin fromVicia villosaseeds (VVLB4). FEBS Lett. 1992, 312, 208–212. [Google Scholar] [CrossRef]
- Hagiwara, K.; Collet-Cassart, D.; Kobayashi, K.; Vaerman, J.P. Jacalin: Isolation, characterization, and influence of various factors on its interaction with human IgA1, as assessed by precipitation and latex agglutination. Mol. Immunol. 1988, 25, 69–83. [Google Scholar] [CrossRef]
- Sanchez, J.-F.; Lescar, J.; Chazalet, V.; Audfray, A.; Gagnon, J.; Alvarez, R.; Breton, C.; Imberty, A.; Mitchell, E.P. Biochemical and Structural Analysis of Helix pomatia Agglutinin. J. Biol. Chem. 2006, 281, 20171–20180. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Dam, T.K.; Gerken, T.A.; Cavada, B.S.; Nascimento, K.S.; Moura, T.R.; Brewer, C.F. Binding Studies of α-GalNAc-specific Lectins to the α-GalNAc (Tn-antigen) Form of Porcine Submaxillary Mucin and Its Smaller Fragments. J. Biol. Chem. 2007, 282, 28256–28263. [Google Scholar] [CrossRef] [Green Version]
- Piller, V.; Piller, F.; Cartron, J.-P. Comparison of the carbohydrate-binding specificities of seven N-acetyl-D-galactosamine-recognizing lectins. Eur. J. Biochem. 1990, 191, 461–466. [Google Scholar] [CrossRef]
- Geisler, C.; DJarvis, L. Letter to the Glyco-Forum: Effective glycoanalysis with Maackia amurensis lectins requires a clear understanding of their binding specificities. Glycobiology 2011, 21, 988–993. [Google Scholar] [CrossRef] [PubMed]
- Shibuya, N.; Goldstein, I.J.; Broekaert, W.F.; Nsimba-Lubaki, M.; Peeters, B.; Peumans, W.J. The elderberry (Sambucus nigra L.) bark lectin recognizes the Neu5Ac(alpha 2-6)Gal/GalNAc sequence. J. Biol. Chem. 1987, 262, 1596–1601. [Google Scholar]
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Costa, V.d.; Mariño, K.V.; Rodríguez-Zraquia, S.A.; Festari, M.F.; Lores, P.; Costa, M.; Landeira, M.; Rabinovich, G.A.; van Vliet, S.J.; Freire, T. Lung Tumor Cells with Different Tn Antigen Expression Present Distinctive Immunomodulatory Properties. Int. J. Mol. Sci. 2022, 23, 12047. https://doi.org/10.3390/ijms231912047
Costa Vd, Mariño KV, Rodríguez-Zraquia SA, Festari MF, Lores P, Costa M, Landeira M, Rabinovich GA, van Vliet SJ, Freire T. Lung Tumor Cells with Different Tn Antigen Expression Present Distinctive Immunomodulatory Properties. International Journal of Molecular Sciences. 2022; 23(19):12047. https://doi.org/10.3390/ijms231912047
Chicago/Turabian StyleCosta, Valeria da, Karina V. Mariño, Santiago A. Rodríguez-Zraquia, María Florencia Festari, Pablo Lores, Monique Costa, Mercedes Landeira, Gabriel A. Rabinovich, Sandra J. van Vliet, and Teresa Freire. 2022. "Lung Tumor Cells with Different Tn Antigen Expression Present Distinctive Immunomodulatory Properties" International Journal of Molecular Sciences 23, no. 19: 12047. https://doi.org/10.3390/ijms231912047