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Tumor Biology

, Volume 36, Issue 2, pp 885–892 | Cite as

α2,6-linked sialic acids on N-glycans modulate the adhesion of hepatocarcinoma cells to lymph nodes

  • Shujing Wang
  • Xixi Chen
  • Anwen Wei
  • Xiao Yu
  • Bachir Niang
  • Jianing Zhang
Research Article

Abstract

The alterations of cell surface sialylation play a key role in tumor metastasis. Enhanced α2,6-sialylation on N-glycans results from overexpression of the sialyltransferase ST6Gal-I. Hca-F and Hca-P cells are murine hepatocarcinoma cell lines which metastasize only to the lymph nodes. Our previous study revealed that ST6Gal-I was involved in the adhesion of Hca-F cells to fibronectin. However, the roles of sialic acids in the adhesion of Hca-F cells to lymph nodes still remain poorly understood. In this study, we observed that expression levels of α2,6-linked sialic acids on Hca-F cells were higher compared to Hca-P cells. Knockdown of ST6Gal-I by small hairpin RNA (shRNA) transfection decreased the expression of α2,6-linked sialic acids and inhibited the adhesion of Hca-F cells to lymph nodes. The adhesion ability was reported to be mediated by siglec-2 which preferentially binds to α2,6-linked sialic acids, and in addition, ST6Gal-I knockdown inhibited the phosphorylated levels of focal adhesion kinase (FAK) and paxillin when cells were treated with siglec-2. Taken together, these results suggest that interaction of α2,6-linked sialic acids with siglec-2 might modulate the adhesion of hepatocarcinoma cells to lymph nodes through the FAK signaling pathway.

Keywords

α2,6-linked sialic acid ST6Gal-I Hepatocarcinoma Adhesion Siglec-2 

Notes

Acknowledgments

This work was supported by grants from the Major State Basic Research Development Program of China (2012CB822103), the National Natural Science Foundation of China (31470799, 31170774), and the Program for Liaoning Excellent Talents in University (LJQ2012079).

References

  1. 1.
    Suzuki O, Abe M. Cell surface N-glycosylation and sialylation regulate galectin-3-induced apoptosis in human diffuse large B cell lymphoma. Oncol Rep. 2008;19:743–8.PubMedGoogle Scholar
  2. 2.
    Li Y, Chen X. Sialic acid metabolism and sialyltransferases: natural functions and applications. Appl Microbiol Biotechnol. 2012;94:887–905.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Takematsu H. Regulation and function of sialic acid modifications in B lymphocytes. Seikagaku. 2010;82:735–40.PubMedGoogle Scholar
  4. 4.
    Bull C, Boltje TJ, Wassink M, de Graaf AM, van Delft FL, den Brok MH, et al. Targeting aberrant sialylation in cancer cells using a fluorinated sialic acid analog impairs adhesion, migration, and in vivo tumor growth. Mol Cancer Ther. 2013;12:1935–46.CrossRefPubMedGoogle Scholar
  5. 5.
    Matsumoto A, Cabral H, Sato N, Kataoka K, Miyahara Y. Assessment of tumor metastasis by the direct determination of cell-membrane sialic acid expression. Angew Chem Int Ed Engl. 2010;49:5494–7.CrossRefPubMedGoogle Scholar
  6. 6.
    Swindall AF, Londono-Joshi AI, Schultz MJ, Fineberg N, Buchsbaum DJ, Bellis SL. ST6Gal-I protein expression is upregulated in human epithelial tumors and correlates with stem cell markers in normal tissues and colon cancer cell lines. Cancer Res. 2013;73:2368–78.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Swindall AF, Bellis SL. Sialylation of the Fas death receptor by ST6Gal-I provides protection against Fas-mediated apoptosis in colon carcinoma cells. J Biol Chem. 2011;286:22982–90.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Lee M, Park JJ, Lee YS. Adhesion of ST6Gal I-mediated human colon cancer cells to fibronectin contributes to cell survival by integrin beta1-mediated paxillin and AKT activation. Oncol Rep. 2010;23:757–61.PubMedGoogle Scholar
  9. 9.
    Wang PH, Lee WL, Lee YR, Juang CM, Chen YJ, Chao HT, et al. Enhanced expression of alpha 2,6-sialyltransferase ST6Gal I in cervical squamous cell carcinoma. Gynecol Oncol. 2003;89:395–401.CrossRefPubMedGoogle Scholar
  10. 10.
    Schultz MJ, Swindall AF, Wright JW, Sztul ES, Landen CN, Bellis SL. ST6Gal-I sialyltransferase confers cisplatin resistance in ovarian tumor cells. J Ovarian Res. 2013;6:25.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Dall'Olio F, Chiricolo M, D'Errico A, Gruppioni E, Altimari A, Fiorentino M, et al. Expression of beta-galactoside alpha2,6 sialyltransferase and of alpha2,6-sialylated glycoconjugates in normal human liver, hepatocarcinoma, and cirrhosis. Glycobiology. 2004;14:39–49.CrossRefPubMedGoogle Scholar
  12. 12.
    Chen WC, Sigal DS, Saven A, Paulson JC. Targeting B lymphoma with nanoparticles bearing glycan ligands of CD22. Leuk Lymphoma. 2012;53:208–10.CrossRefPubMedGoogle Scholar
  13. 13.
    Tedder TF, Poe JC, Haas KM. CD22: a multifunctional receptor that regulates B lymphocyte survival and signal transduction. Adv Immunol. 2005;88:1–50.CrossRefPubMedGoogle Scholar
  14. 14.
    Ji Y, Ling MY, Li Y, Xie H. Effect of cell fusion on metastatic ability of mouse hepatocarcinoma cell lines. World J Gastroenterol. 1999;5:22–4.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Yu S, Zhang L, Li N, Fan J, Liu L, Zhang J, et al. Caveolin-1 up-regulates ST6Gal-I to promote the adhesive capability of mouse hepatocarcinoma cells to fibronectin via FAK-mediated adhesion signaling. Biochem Biophys Res Commun. 2012;427:506–12.CrossRefPubMedGoogle Scholar
  16. 16.
    Jia L, Wang S, Cao J, Zhou H, Wei W, Zhang J. siRNA targeted against matrix metalloproteinase 11 inhibits the metastatic capability of murine hepatocarcinoma cell Hca-F to lymph nodes. Int J Biochem Cell Biol. 2007;39:2049–62.CrossRefPubMedGoogle Scholar
  17. 17.
    Kudo T, Ikehara Y, Togayachi A, Morozumi K, Watanabe M, Nakamura M, et al. Up-regulation of a set of glycosyltransferase genes in human colorectal cancer. Lab Invest. 1998;78:797–811.PubMedGoogle Scholar
  18. 18.
    Recchi MA, Harduin-Lepers A, Boilly-Marer Y, Verbert A, Delannoy P. Multiplex RT-PCR method for the analysis of the expression of human sialyltransferases: application to breast cancer cells. Glycoconj J. 1998;15:19–27.CrossRefPubMedGoogle Scholar
  19. 19.
    Jun L, Yuanshu W, Yanying X, Zhongfa X, Jian Y, Fengling W, et al. Altered mRNA expressions of sialyltransferases in human gastric cancer tissues. Med Oncol. 2012;29:84–90.CrossRefPubMedGoogle Scholar
  20. 20.
    Kaneko Y, Yamamoto H, Kersey DS, Colley KJ, Leestma JE, Moskal JR. The expression of Gal beta 1,4GlcNAc alpha 2,6 sialyltransferase and alpha 2,6-linked sialoglycoconjugates in human brain tumors. Acta Neuropathol. 1996;91:284–92.CrossRefPubMedGoogle Scholar
  21. 21.
    Hsu CC, Lin TW, Chang WW, Wu CY, Lo WH, Wang PH, et al. Soyasaponin-I-modified invasive behavior of cancer by changing cell surface sialic acids. Gynecol Oncol. 2005;96:415–22.CrossRefPubMedGoogle Scholar
  22. 22.
    Schultz MJ, Swindall AF, Bellis SL. Regulation of the metastatic cell phenotype by sialylated glycans. Cancer Metastasis Rev. 2012;31:501–18.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Harduin-Lepers A, Krzewinski-Recchi MA, Colomb F, Foulquier F, Groux-Degroote S, Delannoy P. Sialyltransferases functions in cancers. Front Biosci (EliteEd). 2012;4:499–515.CrossRefGoogle Scholar
  24. 24.
    Liu YC, Yen HY, Chen CY, Chen CH, Cheng PF, Juan YH, et al. Sialylation and fucosylation of epidermal growth factor receptor suppress its dimerization and activation in lung cancer cells. Proc Natl Acad Sci USA. 2011;108:11332–7.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Seales EC, Jurado GA, Brunson BA, Wakefield JK, Frost AR, Bellis SL. Hypersialylation of beta1 integrins, observed in colon adenocarcinoma, may contribute to cancer progression by up-regulating cell motility. Cancer Res. 2005;65:4645–52.CrossRefPubMedGoogle Scholar
  26. 26.
    Hedlund M, Ng E, Varki A, Varki NM. alpha 2-6-Linked sialic acids on N-glycans modulate carcinoma differentiation in vivo. Cancer Res. 2008;68:388–94.CrossRefPubMedGoogle Scholar
  27. 27.
    Pillai S, Netravali IA, Cariappa A, Mattoo H. Siglecs and immune regulation. Annu Rev Immunol. 2012;30:357–92.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Crocker PR, Clark EA, Filbin M, Gordon S, Jones Y, Kehrl JH, et al. Varki, Siglecs: a family of sialic-acid binding lectins. Glycobiology 8, (1998) v.Google Scholar
  29. 29.
    Poe JC, Tedder TF. CD22 and Siglec-G in B cell function and tolerance. Trends Immunol. 2012;33:413–20.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Nitschke L. CD22 and Siglec-G: B-cell inhibitory receptors with distinct functions. Immunol Rev. 2009;230:128–43.CrossRefPubMedGoogle Scholar
  31. 31.
    Schaller MD. Cellular functions of FAK kinases: insight into molecular mechanisms and novel functions. J Cell Sci. 2010;123:1007–13.CrossRefPubMedGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Shujing Wang
    • 1
  • Xixi Chen
    • 1
  • Anwen Wei
    • 1
  • Xiao Yu
    • 2
  • Bachir Niang
    • 1
  • Jianing Zhang
    • 1
    • 3
  1. 1.Department of Biochemistry, Institute of GlycobiologyDalian Medical UniversityDalianChina
  2. 2.Department of PathologyDalian Medical UniversityDalianChina
  3. 3.School of Life Science and MedicineDalian University of TechnologyDalianChina

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