Galektinler ve Mide Kanseri

Yıl 2024, Cilt: 5 Sayı: 1, 8 - 15, 30.01.2024

Ayşe Aksu , İlhan Yaylım

Öz

Mide kanseri ülkelere göre histopatolojik ve epidemiyolojik farklılıklar gösteren hete¬rojen bir kanser türüdür
ve dünya genelinde yaygın olarak görülmektedir. Mide
kanseri Helicobacter pylori ve Epstein-Barr virüsü (EBV)
enfeksiyonları gibi mikrobiyal, aile öyküsü, A kan grubu,
E-kaderin gen mutasyonu içeren genetik ve sigara, alkol
tüketimi, yağ, karbonhidrat, nitrat ve tuz oranı yüksek gıda
tüketimi gibi çevresel faktörlerin etkisiyle ortaya çıkabilen
bir kanser türüdür. Mide kanserinde hayatta kalma oranlarının düşük olması nedeniyle; ileri evre mide kanserine
yönelik alternatif tedavilerin geliştirilmesi önemlidir. Günümüzde, kemoterapi, radyoterapi, immünoterapi alanlarında gerçekleşen ilerlemelere karşın iyileşme için ilk tercih genellikle cerrahi tedavidir Galektinler, 130 amino asit
(aa) barındıran karbonhidrat tanıma sahaları (crd) içerisinde evrimsel olarak korunmuş β –galaktozidleri bağlayan bir protein sınıfı olarak tanımlanır. Günümüze kadar
12 tanesi insanlarda olmak üzere memelilerde 16 farklı
Galektin tanımlanmıştır. Galektinler, yapısal özelliklerine ve polipeptit zincirin CRD sayılarına göre; Prototipik
(Gal-1,-2,-5,-7,-10,-11,-13,-14) Tandem-Tekrar (Gal-4,-
2,-8,-9,-12) ve Kimera (Gal-3) olmak üzere üç alt grupta
toplanır. Lektin ailesi üyelerinden Galektinler; tümör mikro çevresinde yüksek oranda bulunması, hücre göçü, kanserle ilgili birçok sinyal iletimi ve immün sistemin düzenlenmesinde görev alması gibi özellikleri nedeniyle kanser
çalışmalarında araştırılan proteinlerdir. Mide kanserinin
oluşum ve gelişim mekanizmasının daha iyi anlaşılması,
kişiye özel terapilerin ve hedefe yönelik potansiyel biyobelirteçlerin belirlenmesi amacıyla başta Gal-3 olmak üzere
moleküler düzeyde mide kanseri ile ilişkisinin anlaşılabilmesi ve aynı şekilde, Gal-4, Gal-7 Gal-9 gibi diğer Galektin
üyelerinin de mide ve diğer kanser türlerindeki rolünü belirlenebilmesi, tanı ve tedavi süreçlerine etkisinin anlaşılabilmesi için daha ileri çalışmalara ihtiyaç duyulmaktadır.

Anahtar Kelimeler

mide kanseri, galektin, biyobelirteç

Kaynakça

• 1.Sung, H., Ferlay, J., Siegel, R. L., Laver-sanne, M., Soerjomataram, I., Jemal, A., & Bray, F. (2021). Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: a cancer journal for cli-nicians, 71(3), 209-249.
• 2. Chia NY, Tan P. Molecular classification of gastric cancer. Ann Oncol. 2016 May;27(5):763-9.
• 3. Ajani, J. A. et al. Gastric cancer, version 2. 2022, NCCN clinical practice guidelines in oncology. J. Natl Compr. Canc. Netw. 20, 167–192 (2022).
• 4. Ilic, M. & Ilic, I. Epidemiology of stomach cancer. World J. Gastroenterol. 28,1187–1203 (2022).
• 5. Wang, Z. et al. Identification of new sus-ceptibility loci for gastric non-cardia ade-nocarcinoma: pooled results from two Chinese genome-wide association studies. Gut 66, 581–587 (2017)
• 6. Chen YC, Fang WL, Wang RF, Liu CA, Yang MH, Lo SS, Wu CW, Li AF, Shyr YM, Huang KH. Clinicopathological Variation of Lauren Classification in Gastric Cancer. Pathol Oncol Res. 2016 Jan;22(1):197-202.
• 7. Hu B, El Hajj N, Sittler S, Lammert N, Bar-nes R, Meloni-Ehrig A. Gastric cancer: Classification, histology and application of molecular pathology. J Gastrointest Oncol. 2012 Sep;3(3):251-61.
• 8. Rugge M; Fassan M; Graham DY Epide-miology of Gastric Cancer. Gastric Cancer. 2015 23–34.
• 9. Ahn JS, Eom CS, Jeon CY, et al: Acid suppressive drugs and gastric cancer: A meta-analysis of observational studies. World J Gastroenterol 19: p. 2560-2568,2013.
• 10. Plummer, M., Franceschi, S., Vignat, J., Forman, D. & de Martel, C. Global burden of gastric cancer attributable to Helicobac-ter pylori. Int. J. Cancer 136, 487–490 (2015).Classification, histology and application of molecular pathology. J Gastrointest Oncol. 2012 Sep;3(3):251-61.
• 11. Fock, K. M. Review article: the epidemio-logy and prevention of gastric can-cer. Aliment Pharmacol. Ther. 40, 250–260 (2014)
• 12. De Manzoni, G. & Roviello, F. Gastric Can-cer: the 25-year R-Evolution (Springer,2021).
• 13. Baj J., Brzozowska K., Forma A., Maani A., Sitarz E., Portincasa P. Immunological Aspects of the Tumor Microenvironment and Epithelial-Mesenchymal Transition in Gastric Carcinogenesis. Int. J. Mol. Sci. 2020;21:2544.
• 14. Baj J., Korona-Glowniak I., Forma A., Ma-ani A., Sitarz E., Rahnama-Hezavah M., Radzikowska E., Portincasa P. Mechanisms of the Epithelial–Mesenchymal Transition and Tumor Microenvironment in Helicobacter pylori-Induced Gastric Cancer. Cells. 2020;9:1055.
• 15. Moy K.A., Fan Y., Wang R., Gao Y.-T., Yu M.C., Yuan J.-M. Alcohol and tobacco use in relation to gastric cancer: A prospective study of men in Shanghai, China. Cancer Epidemiol. Biomark. Prev. 2010;19:2287–2297.
• 16. Stahl P; Seeschaaf C; Lebok P; et al. He-terogeneity of amplification of HER2, EGFR, CCND1 and MYC in gastric cancer. BMC Gastroenterol. 2015;15:7 Published 2015 Feb 5.
• 17. Tan Z. Recent Advances in the Surgical Treatment of Advanced Gastric Cancer: A Review. Med Sci Monit. 2019 May 13;25:3537-3541.
• 18. Digklia A, Wagner AD. Advanced gastric cancer: Current treatment landscape and future perspectives. World J Gastroente-rol. 2016;22(8):2403–14.
• 19. Das M. Neoadjuvant chemotherapy: survi-val benefit in gastric cancer. Lancet Oncol. 2017;18(6):e307.
• 20. Lv X, Zhang L, Huang R, Song W. A clini-cal exploration of neoadjuvant chemothe-rapy with tegafur, gimeracil, and oteracil potassium capsules combined with oxaliplatin for advanced gastric cancer. Int J Clin Exp Med. 2015;8(10):19030–36.
• 21. Barondes, S. H. et al. Galectins: A family of animal β-galactoside-binding lectins. Cell 76, 597–598 (1994).
• 22. Brinchmann MF, Patel DM, Iversen MH. The Role of Galectins as Modulators of Metabolism and Inflammation. Mediators Inflamm. 2018;2018:9186940.
• 23. Cummings, RD, Liu, FT, and Vasta, GR. Galectins. In: rd, A Varki, RD Cummings, JD Esko, P Stanley and GW Hartet al., edi-tors. Essentials of Glycobiology. Cold Spring Harbor (NY) (2015). p. 469–480.
• 24.Lewis, SK, Farmer, JL, Burghardt, RC, Newton, GR, Johnson, GA, Adelson, DL, et al. Galectin 15 (LGALS15): a gene uniquely expressed in the uteri of sheep and goats that functions in trophoblast at-tachment. Biol Reprod. (2007)
• 25. Farhad, M., Rolig, A. S. & Redmond, W. L. The role of Galectin-3 in modulating tumor growth and immunosuppression within the tumor microenvironment. Oncoimmu-nology 7, e1434467 (2018).
• 26. Fortuna-Costa, A., Gomes, A. M., Koz-lowski, E. O., Stelling, M. P. & Pavão, M. SG. Extracellular Galectin-3 in Tumor Progression and Metastasis. Front. Oncol. 4, (2014).
• 27. Girotti, MR, Salatino, M, Dalotto-Moreno, T, and Rabinovich, GA. Sweetening the hallmarks of cancer: Galectins as multi-functional mediators of tumor progres-sion. J Exp Med. (2020) 217:e20182041.
• 28. Johannes, L, Jacob, R, and Leffler, H. Ga-lectins at a glance. J Cell Sci. (2018) 131:cs208884.
• 29. Liu D, Zhu H, Li C. Galectins and galectin-mediated autophagy regulation: new in-sights into targeted cancer therapy. Bio-mark Res. 2023 Feb 22;11(1):22.
• 30. Camby I, Le Mercier M, Lefranc F and Kiss R: Galectin 1: A small protein with major functions. Glycobiology 16: 137R 157R, 2006.
• 31. Carlini MJ, Roitman P, Nuñez M, Pallotta MG, Boggio G, Smith D, Salatino M, Joffé ED, Rabinovich GA and Puricelli LI: Clini-cal relevance of galectin 1 expression in non small cell lung cancer patients. Lung Cancer 84: 73 78, 2014.
• 32. Huang CS, Tang SJ, Chung LY, Yu CP, Ho JY, Cha TL, Hsieh CC, Wang HH, Sun GH and Sun KH: Galectin 1 upregulates CXCR4 to promote tumor progression and poor outcome in kidney cancer. J Am Soc Nephrol 25: 1486 1495, 2014.
• 33. Zhang PF, Li KS, Shen YH, Gao PT, Dong ZR, Cai JB, Zhang C, Huang XY, Tian MX, Hu ZQ, et al: Galectin 1 induces hepato cellular carcinoma EMT and sorafenib re-sistance by activating FAK/PI3K/AKT sig-naling. Cell Death Dis 7: e2201, 2016. In-ternatıonal Journal Of Oncology 61: 141, 2022 17
• 34. Schulz H, Schmoeckel E, Kuhn C, Hof-mann S, Mayr D, Mahner S and Jeschke U: Galectins 1, 3, and 7 are prognostic markers for survival of ovarian cancer pa-tients. Int J Mol Sci 18: 1230, 2017.
• 35. Elola MT, Wolfenstein Todel C, Troncoso MF, Vasta GR and Rabinovich GA: Galec-tins: Matricellular glycan binding proteins linking cell adhesion, migration, and sur-vival. Cell Mol Life Sci 64: 1679 1700, 2007
• 36. You X, Liu Q, Wu J, Wang Y, Dai J, Chen D, Zhou Y, Lian Y. Galectin-1 Promotes Vasculogenic Mimicry in Gastric Cancer by Upregulating EMT Signaling. J Cancer. 2019 Oct 17;10(25):6286-6297.PMID:31772662; PMCID: PMC6856752.
• 37. Okada, K.; Shimura, T.; Suehiro, T.; Moc-hiki, E.; Kuwano, H. Reduced galectin-3 expression is an indicator of unfavorable prognosis in gastric cancer. Anticancer Res. 2006, 26, 1369–1376.
• 38. Dong, R.; Zhang, M.; Hu, Q.; Zheng, S.; Soh, A.; Zheng, Y.; Yuan, H. Galectin-3 as a novel biomarker for disease diagnosis and a target for therapy (Review). Int. J. Mol. Med. 2017, 41, 599–614.
• 39. Newlaczyl, A.U.; Yu, L.-G. Galectin-3—A jack-of-all-trades in cancer. Cancer Lett. 2011, 313, 123–128
• 40. de Oliveira, J.T.; de Matos, A.J.; Gomes, J.; Vilanova, M.; Hespanhol, V.; Manninen, A.; Rutteman, G.; Chammas, R.; Gärtner, F.; Bernardes, E.S. Coordinated expression of galectin-3 and galectin-3-binding sites in malignant mammary tumors: Implicati-ons for tumor metastasis. Glycobiology 2010, 20, 1341–1352.
• 41. Thijssen, V.L.; Heusschen, R.; Caers, J.; Griffioen, A.W. Galectin expression in cancer diagnosis and prognosis: A syste-matic review. Biochim. Biophys. Acta-Rev. Cancer 2015, 1855, 235–247.
• 42.Wang, C.; Zhou, X.; Ma, L.; Zhuang, Y.; Wei, Y.; Zhang, L.; Jin, S.; Liang, W.; Shen, X.; Li, C.; et al. Galectin-3 may serve as a marker for poor prognosis in colorectal cancer: A meta-analysis. Pathol.-Res. Pract. 2019, 215, 152612.
• 43. Shao, Q.; He, J.; Chen, Z.; Wu, C. Prognos-tic role of galectins expression in patients with hepatic cancer. Medicine 2020, 99, e19622.
• 44. Long, B.; Yu, Z.; Zhou, H.; Ma, Z.; Ren, Y.; Zhan, H.; Li, L.; Cao, H.; Jiao, Z. Clinical characteristics and prognostic significance of galectins for patients with gastric cancer: A meta-analysis. Int. J. Surg. 2018, 56, 242–249.
• 45. Sturm A, Lensch M, André S, Kaltner H, Wiedenmann B, Rosewicz S, Dignass AU, Gabius HJ. Human galectin-2: novel indu-cer of T cell apoptosis with distinct profile of caspase activation. J. Immunol. 2004;173:3825–3837.
• 46. Kim SW, Park KC, Jeon SM, Ohn TB, Kim T, Il, Kim WH, Cheon JH. Abrogation of galectin-4 expression promotes tumorige-nesis in colorectal cancer. Cell. Oncol. 2013;36:169–178.
• 47. Paclik D, Lohse K, Wiedenmann B, Dig-nass AU, Sturm A. Galectin-2 and-4, but not galectin-1, promote intestinal epithelial wound healing in vitro through a TGF-beta-independent mechanism. Inflamm. Bowel. Dis. 2008;14:1366–1372.
• 48. McCullough PA, Olobatoke A, Vanhecke TE. Galectin-3: a novel blood test for the evaluation and management of patients with heart failure. Rev Cardiovasc Med. 2011;12(4):200-10. doi: 10.3909/ricm0624.
• 49. Kawachi K, Matsushita Y, Yanezawa S, Nakano S, Shirao K, Natsugoe S, et al. Galectin-3 expression in various thyroid neoplasms and its possible role in metastasis formation. Hum Pathol 2000; 31: 428-433
• 50. Barrès C, Blanc L, Bette-Bobillo P, André S, Mamoun R, Gabius HJ, Vidal M. Galec-tin-5 is bound onto the surface of rat reti-culocyte exosomes and modulates vesicle uptake by macrophages. Blood. 2010;115:696–705.
• 51. Skutelsky E, Bayer EA. Cell-type-related segregation of surface galactosyl-containing components at an early deve-lopmental stage in hemopoietic bone marrow cells in the rabbit. J. Cell Biol. 1983;96:184–190.
• 52. Gitt MA, Colnot C, Poirier F, Nani KJ, Ba-rondes SH, Leffler H. Galectin-4 and ga-lectin-6 are two closely related lectins expressed in mouse gastrointestinal tract. J. Biol. Chem. 1998;273:2954–2960.
• 53. Nio-Kobayashi J. Tissue- and cell-specific localization of galectins, beta-galactose-binding animal lectins, and their potential functions in health and disease. Anat. Sci. Int. 2017;92:25–36.
• 54. Saussez S, Kiss R. Galectin-7. Cell Mol. Li-fe Sci. : CMLS. 2006;63:686–697
• 55. Brewer CF. Thermodynamic binding stu-dies of galectin-1, -3 and -7. Glycoconj J. 2004; 19(7-9):459-465.
• 56. Cao Z, Said N, Amin S, Wu H, Bruce A, Garate M, Hsu D, Kuwabara I, Liu F and Panjwani N. Galectins-3 and -7, but not galectin-1, play a role in re-epithelialization of wounds. J Biol Chem. 2002; 277(44):42299-42305
• 57. Gendronneau G, Sidhu S, Delacour D, Dang T, Calonne C, Houzelstein D, Mag-naldo T and Poirier F. Galectin-7 in the control of epidermal homeostasis after in-jury. Mol Biol Cell. 2008; 19(12):5541-5549. Epub 2008 Oct 5541
• 58.Hadari YR, Arbel-Goren R, Levy Y, Ams-terdam A, Alon R, Zakut R, Zick Y. Galec-tin-8 binding to integrins inhibits cell ad-hesion and induces apoptosis. J. Cell. Sci. 2000;113(Pt 13):2385–2397.
• 59. Rabinovich GA, Toscano MA. Turning ‘sweet’ on immunity: galectin-glycan inte-ractions in immune tolerance and inf-lammation. Nat. Rev. Immunol. 2009;9:338–352.
• 60. Heusschen, R.; Griffioen, A.W.; Thijssen, V.L. Galectin-9 in tumor biology: A jack of multiple trades. Biochim. Biophys. Acta-Rev. Cancer 2013, 1836, 177–185.
• 61. Kerr, J.F.; Wyllie, A.H.; Currie, A.R. Apop-tosis: A basic biological phenomenon with wide-ranging implications in tissue kine-tics. Br. J. Cancer 1972, 26, 239– 257.
• 62. Galluzzi, L.; Vitale, I.; Abrams, J.M.; Al-nemri, E.S.; Baehrecke, E.H.; Blagosk-lonny, M.V.; Dawson, T.M.; Dawson, V.L.; El-Deiry, W.S.; Fulda, S.; et al. Molecular definitions of cell death subrou-tines: Recommendations of the Nomenc-lature Committee on Cell Death 2012. Cell Death Differ. 2012, 19, 107–120.
• 63. Plati, J.; Bucur, O.; Khosravi-Far, R. Dysre-gulation of apoptotic signaling in cancer: Molecular mechanisms and therapeutic opportunities. J. Cell. Biochem. 2008, 104, 1124–1149.
• 64. Vladoiu, M.C.; Labrie, M.; St-Pierre, Y. Int-racellular galectins in cancer cells: Poten-tial new targets for therapy (Review). Int. J. Oncol. 2014, 44, 1001–1014.
• 65. Ackerman SJ, Weil GJ, Gleich GJ. Forma-tion of Charcot-Leyden crystals by human basophils. J. Exp. Med. 1982;155:1597–1609.
• 66. Kubach J, Lutter P, Bopp T, Stoll S, Becker C, Huter E, Richter C, Weingarten P, War-ger T, Knop J, Mullner S, Wijdenes J, Schild H, Schmitt E, Jonuleit H. Human CD4+CD25+ regulatory T cells: proteome analysis identifies galectin-10 as a novel marker essential for their anergy and suppressive function. Blood. 2007;110:1550–1558
• 67. Dunphy JL, Balic A, Barcham GJ, Horvath AJ, Nash AD, Meeusen EN. Isolation and characterization of a novel inducible mammalian galectin. J. Biol. Chem. 2000;275:32106–32113
• 68. Yang RY, Hsu DK, Yu L, Chen HY, Liu FT. Galectin-12 is required for adipogenic signaling and adipocyte differentiation. J. Biol. Chem. 2004;279:29761–29766.
• 69. Than NG, Balogh A, Romero R, Karpati E, Erez O, Szilagyi A, Kovalszky I, Sammar M, Gizurarson S, Matko J, Zavodszky P, Papp Z, Meiri H. Placental Protein 13 (PP13) - A Placental Immunoregulatory Galectin Protecting Pregnancy. Front. Im-munol. 2014;5:348
• 70. Young AR, Barcham GJ, Kemp JM, Dunphy JL, Nash A, Meeusen EN. Functi-onal characterization of an eosinophil-specific galectin, ovine galectin-14. Glyco-conj. J. 2009;26:423–432.