Lectin Treatment Affects Malignant Characteristics of TPC-1 Papillary Thyroid Cancer Cells

Year 2019, Volume: 78 Issue: 1, 51 - 57, 31.05.2019

Aylin Sancakli Engin Kaptan

Abstract

Objective: Abnormal glycosylation is a universal aspect of cancer cells. The altered glycosylation pattern has been originated from changings in expression of glycosylation enzymes which are up-regulating in reply to some oncoproteins in the biosynthetic pathway of glycans. In this study, it was aimed to show the presence of terminal α-2,3, α-2,6 sialic acid and α-1,6/α-1,2 fucose motifs in TPC-1 papillary thyroid cancer cells. Also it was aimed to examine the changes in viability and mobility of the cells after exogenously specific lectin treatment.

Materials and Methods: In this study, the presence of terminal sugar residues in glycan chains on the cell surface was demonstrated using lectin histochemistry and lectin blotting techniques in TPC-1 cells. The changes in the cell viability and proliferation after lectin treatment were assessed using the WST-1 test. The Changes in the cell mobility after lectin treatment, however, were assessed using the wound healing test. 

Results: α-2,3, α-2,6 sialic acid and α-1,6/α-1,2 fucose motifs were widespread in the surface of TPC-1 cells. MAL-II (Maackia amurensis Lectin II) treatment increased the cell proliferation and mobility of TPC-1 cells. Although SNA (Sambucus nigra Aglutinin) and AAL (Aleuria aurantia Lectin) treatment did not significantly affect the cell proliferation, SNA and AAL treatment supported the mobility of TPC-1 cells.

Conclusion: Lectin treatment affect cancerous properties differently depending on the cell type. Also lectin treatment can support the malignant behaviour of cancer. For this reason, it is necessary to understand the mechanisms of the lectin effect on the cancer cells.

Keywords

Papillary thyroid cancer, lectin treatment, glycosylation

References

• 1. Xing M. Molecular pathogenesis and mechanisms of thyroid cancer. Nat Rev Cancer 2013; 13(3):184-99.
• 2. Catalano MG, Poli R, Pugliese M, Fortunati N, Boccuzzi G. Emerging molecular therapies of advanced thyroid cancer. Mol Aspects Med 2010; 31(2): 215-26.
• 3. KondoT, Ezzat S, Asa SL. Pathogenetic mechanisms in thyroid follicular-cell neoplasia. Nat Rev Cancer 2006; 6(4): 292-306.
• 4. Xing M. Prognostic utility of BRAF mutation in papillary thyroid cancer. Mol Cell Endocrinol 2010; 321(1): 86-93.
• 5. Nucera C, Lawler J, Hodin R, Parangi S. The BRAFV600E mutation: what is it really orchestrating in thyroid cancer? Oncotarget 2010; 1(8): 751-6.
• 6. Janknecht R. On the road to immortality: hTERT upregulation in cancer cells. FEBS Lett 2004; 564(1-2): 9-13.
• 7. Bodnar AG, Ouellette M, Frolkis M, Holt SE, Chiu CP, Morin GB, Harley CB, Shay JW, Lichtsteiner S, Wright WE,. Extension of life-span by introduction of telomerase into normal human cells. Science 1998; 279(5349): 349-52.
• 8. Hrdličková R, Nehyba J, Bose HR. Alternatively spliced telomerase reverse transcriptase variants lacking telomerase activity stimulate cell proliferation. Mol Cell Biol 2012; 32(21): 4283-96.
• 9. Sarin KY, Cheung P, Gilison D, Lee E, Tennen RI, Wang E, Artandi MK, Oro AE, Artandi SE. Conditional telomerase induction causes proliferation of hair follicle stem cells. Nature 2005; 436(7053): 1048-52
• 10. Reinders J, Sickmann A. Modificomics: posttranslational modifications beyond protein phosphorylation and glycosylation. Biomol Eng 2007; 24(2): 169-77.
• 11. Freeze HH, Chong JX, Bamshad MJ, Ng BG. Solving glycosylation disorders: fundamental approaches reveal complicated pathways. Am J Hum Genet 2014; 94(2): 161-75.
• 12. Schultz MJ, Swindall AF, Bellis SL. Regulation of the metastatic cell phenotype by sialylated glycans. Cancer Metastasis Rev 2012; 31(3-4): 501-18.
• 13. Reis CA, Osorio H, Silva L, Gomes C, David L. Alterations in glycosylation as biomarkers for cancer detection. J Clin Pathol 2010; 63(4): 322-9.
• 14. A. Varki, R. Kannagi, and B. P. Toole, “Glycosylation changes in cancer” in Essentials of Glycobiology, A. Varki, R. D. Cummings, J. D. Esko et al., Eds., 2009.
• 15. Meany DL, Chan DW. Aberrant glycosylation associated with enzymes as cancer biomarkers. Clin Proteom 2011; 8(1): 7.
• 16. Martin LT, Marth JD, Varki A, Varki NM. Genetically altered mice with different sialyltransferase deficiencies show tissue-specific alterations in sialylation and sialic acid 9-O-acetylation. J Biol Chem 2002; 277(36): 32930-8.
• 17. De Mejía, E.G. and Prisecaru, V.I., (2005). Lectins as bioactive plant proteins: a potential in cancer treatment. Crit Rev Food Sci Nutr 45(6): 425-45.
• 18. Ryder SD, Smith JA, Rhodes JM. Peanut lectin: a mitogen for normal human colonic epithelium and human HT29 colorectal cancer cells. J Natl Med Assoc 1992; 84(18): 1410-6.
• 19. Singh R, Subramanian S, Rhodes JM, Campbell BJ. Peanut lectin stimulates proliferation of colon cancer cells by interaction with glycosylated CD44v6 isoforms and consequential activation of c-Met and MAPK: functional implications for disease-associated glycosylation changes. Glycobiology 2006; 16(7): 594-601.
• 20. Mehta S, Chhetra R, Srinivasan R, Sharma SC, Behera D. Ghosh S. Potential importance of Maackia amurensis agglutinin in non-small cell lung cancer. Biol Chem 2013; 394(7): 889-900.
• 21. Chen J, Liu B, Ji N, Zhou J, Bian HJ, Li CY, Chen F, Bao JK, A novel sialic acid-specific lectin from Phaseolus coccineus seeds with potent antineoplastic and antifungal activities. Phytomedicine 2009; 16(4): 352-60.
• 22. Liu Z, Liu B, Zhang ZT, Zhou TT, Bian HJ, Min MW, Liu YH, Chen J, Bao JK. A mannose-binding lectin from Sophora flavescens induces apoptosis in HeLa cells. Phytomedicine 2008; 15(10): 867-75.
• 23. Hagiwara K, Collet-Cassart D, Kunihiko K, Vaerman JP. 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(1): 69-83.
• 24. Ahmed H, Chatterjee BP. Further characterization and immunochemical studies on the carbohydrate specificity of jackfruit (Artocarpus integrifolia) lectin. J Biol Chem 1989; 264(16): 9365-72.
• 25. Yu LG, Milton JD, Fernig DG, Rhodes JM. Opposite effects on human colon cancer cell proliferation of two dietary Thomsen‐Friedenreich antigen‐binding lectins. J Cell Physiol 2001; 186(2): 282-7.
• 26. Wang Q, Yu LG, Campbell BJ, Milton JD, Rhodes JM. Identification of intact peanut lectin in peripheral venous blood. Lancet 1998; 352(9143): 1831-2.
• 27. Ochoa-Alvarez JA, Krishnan H, Pastorino JG, Nevel E, Kephart D, Lee JJ, Retzbach EP, Shen Y, Fatahzadeh M, Baredes S, Kalyoussef E. Antibody and lectin target podoplanin to inhibit oral squamous carcinoma cell migration and viability by distinct mechanisms. Oncotarget 2015; 6(11): 9045-60.
• 28. Kolasińska E, Przybyło M, Janik M, Lityńska A. Towards understanding the role of sialylation in melanoma progression. Acta Biochim Pol 2016; 63(3): 533-41.
• 29. Kaptan E, Sancar‐Bas S, Sancakli A, Bektas S, Bolkent S. The effect of plant lectins on the survival and malignant behaviors of thyroid cancer cells. J Cell Biochem 2018; 119(7): 6274-87.