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

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Tumor Biology

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.

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References

  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.

    CAS  PubMed  Google Scholar 

  2. Li Y, Chen X. Sialic acid metabolism and sialyltransferases: natural functions and applications. Appl Microbiol Biotechnol. 2012;94:887–905.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Takematsu H. Regulation and function of sialic acid modifications in B lymphocytes. Seikagaku. 2010;82:735–40.

    CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  22. Schultz MJ, Swindall AF, Bellis SL. Regulation of the metastatic cell phenotype by sialylated glycans. Cancer Metastasis Rev. 2012;31:501–18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  27. Pillai S, Netravali IA, Cariappa A, Mattoo H. Siglecs and immune regulation. Annu Rev Immunol. 2012;30:357–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

  29. Poe JC, Tedder TF. CD22 and Siglec-G in B cell function and tolerance. Trends Immunol. 2012;33:413–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Nitschke L. CD22 and Siglec-G: B-cell inhibitory receptors with distinct functions. Immunol Rev. 2009;230:128–43.

    Article  CAS  PubMed  Google Scholar 

  31. Schaller MD. Cellular functions of FAK kinases: insight into molecular mechanisms and novel functions. J Cell Sci. 2010;123:1007–13.

    Article  CAS  PubMed  Google Scholar 

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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).

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Correspondence to Jianing Zhang.

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Shujing Wang and Xixi Chen contributed equally to this work.

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Wang, S., Chen, X., Wei, A. et al. α2,6-linked sialic acids on N-glycans modulate the adhesion of hepatocarcinoma cells to lymph nodes. Tumor Biol. 36, 885–892 (2015). https://doi.org/10.1007/s13277-014-2638-x

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  • DOI: https://doi.org/10.1007/s13277-014-2638-x

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