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Inhibition by Imatinib of Expression of O-glycan-related Glycosyltransferases and Tumor-associated Carbohydrate Antigens in the K562 Human Leukemia Cell Line

  • Sun, Qi-Chang ;
  • Liu, Mi-Bo ;
  • Shen, Hong-Jie ;
  • Jiang, Zhi ;
  • Xu, Lan ;
  • Gao, Li-Ping ;
  • Ni, Jian-Long ;
  • Wu, Shi-Liang
  • Published : 2013.04.30

Abstract

Objective: To study changes of tumor associated carbohydrate antigen (TACAs) expression and mRNA levels for tumor associated glycosyltransferases, and assess subcellular localizations of N-acetyl galactosyltransferases (GalNAc-Ts) in the K562 leukemia cell line after imatinib treatment. Methods: RT-PCR was performed to analyze the expression of glycosyltransferases which synthesize O-glycan in tumor-associated carbohydrate antigens (TCTAs). The expression of Tn antigen, T antigen and sialyl T antigen on K562 cell membranes was measured by flow cytometry after treatment with different concentrations of imatinib. Co-localization of GalNAc-Ts and ER (endoplasmic reticulum) was determined by confocal laser scanning microcopy. Results: Transcript expression levels of several glycosyltransferases related to TCTAs were decreased after imatinib ($0-0.3{\mu}M$) treatment. Expression of Tn antigen and T antigen was increased while that of sialyl T antigen was decreased. Co-localization of GalNAc-Ts and ER was reduced by $0.2{\mu}M$ of imatinib. Conclusion: Imatinib inhibited the expression of O-glycan related TACAs and several related glycosyltransferases, while decreasing the co-localization of GalNAc-Ts and ER and normalizing O-glycosylation in the K562 human leukemia cell.

Keywords

Imatinib;K562;glycosyltransferases;tumor-associated carbohydrate antigens;leukemia cells

References

  1. Boggon TJ, Eck MJ (2004). Structure and regulation of Src family kinases. Oncogene, 23, 7918-27. https://doi.org/10.1038/sj.onc.1208081
  2. Brockhausen I (2006). Mucin-type O-glycans in human colon and breast cancer: glycodynamics and functions. EMBO Rep, 7, 599-604. https://doi.org/10.1038/sj.embor.7400705
  3. Brockhausen I, Dowler T, Paulsen H (2009). Site directed processing: Role of amino acid sequences and glycosylation of acceptor glycopeptides in the assembly of extended mucin type O-glycan core 2. Biochim Biophysica Acta, 1790, 1244-57. https://doi.org/10.1016/j.bbagen.2009.05.020
  4. Buchdunger E, Zimmermann J, Mett H, et al (1996). Inhibition of the Abl protein-tyrosine kinase in vitro and in vivo by a 2-phenylaminopyrimidine derivative. Cancer Res, 56, 100 4.
  5. Danhauser-Riedl S, Warmuth M, Druker BJ, et al (1996). Activation of Src kinases p53/56lyn and p59hck by p210bcr/ abl in myeloid cells. Cancer Res, 56, 3589-96.
  6. Deininger MWN, Goldman JM, Lydon N, Melo JV (1997). The tyrosine kinase inhibitor CGP57148B selectively inhibits the growth of BCRABL-positive cells. Blood, 90, 3691-8.
  7. Faderl S, Talpaz M, Estrov Z, Kantarjian HM (1999). Chronic myelogenous leukemia: biology and therapygh. Ann Int Med, 131, 207 19.
  8. Gerken TA, Owens CL, Pasumarthy M (1998). Site-specific core 1 O-glycosylation pattern of the porcine submaxillary gland mucin tandem repeat Evidence for the modulation of glycan length by peptide sequence. J Biol Chem, 273, 26580-8. https://doi.org/10.1074/jbc.273.41.26580
  9. Gill DJ, Chia J, Senewiratne J, et al (2010). Regulation of O-glycosylation through Golgi-to-ER relocation of initiation enzymes. J Cell Biol, 189, 843-58. https://doi.org/10.1083/jcb.201003055
  10. Hakomori S (1985). Aberrant glycosylation in cell membranes as focused on glycolipids:overview and perspectives. Cancer Res, 45, 2405-14.
  11. Hakomori S (1996). Tumor malignancy defined by aberrant glycosylation and sphingo(glyco)lipid metabolism. Cancer Res, 56, 5309-18.
  12. Heimburg-Molinaro J, Lum M, Vijay G, et al (2011). Cancer vaccines and carbohydrate epitopes. Vaccine, 29, 8802-26. https://doi.org/10.1016/j.vaccine.2011.09.009
  13. Hitomi T, Seiichi T, Michiie S, et al (2003). Aberrant O-glycosylation inhibits stable expression of dysadherin, a carcinoma-associated antigen, and facilitates cell-cell adhesion. Glycobiology, 13, 521-7 https://doi.org/10.1093/glycob/cwg065
  14. Lionberger JM, Wilson MB, Smithgall TE (2000). Transformation of myeloid leukemia cells to cytokine independence by Bcr-Abl is suppressed by kinase-defective Hck. J Biol Chem, 275, 18581-5. https://doi.org/10.1074/jbc.C000126200
  15. Liu C, Lin D, Xu L, et al (2011). An anti-human ppGalNAcT-2 monoclonal antibody. Hybridoma, 30, 549-54. https://doi.org/10.1089/hyb.2011.0022
  16. Lozzio CB, Lozzio BB (1975). Human chronic myelogenous leukemia cell-line with positive Philadelphia chromosome, Blood, 45, 321-34.
  17. Quint s-Cardama A, Cortes J (2009). Molecular biology of bcr-abl1 positive chronic myeloid leukemia. Blood, 113, 1619-30. https://doi.org/10.1182/blood-2008-03-144790
  18. Reis CA, Osorio H, Silva L, et al (2010). Alterations in glycosylation as biomarkers for cancer detection. J Clin Pathol, 63, 322-9. https://doi.org/10.1136/jcp.2009.071035
  19. Warmuth M, Bergmann M, Priess A, et al (1997). The Src family kinase Hck interactswith Bcr-Abl by a kinase-independent mechanism and phosphorylates the Grb2-binding site of Bcr. J Biol Chem, 272, 33260-70. https://doi.org/10.1074/jbc.272.52.33260
  20. Yamada K, Mitsui Y, Kakoi N, et al (2012). One-pot characterization of cancer cells by the analysis of mucintype glycans and glycosaminoglycan. Anal Biochem, 421, 595-606. https://doi.org/10.1016/j.ab.2011.12.017

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