Nilsen YILDIRIM ERDOĞAN, Gülben ERDEM HUQ, Melin GECER

442153

GALEKTİN-3’ÜN KOLON KARSİNOM METASTAZINDAKİ YERİ VE ÖNEMİ

Amaç: Galektin-3, hücre içi ve hücre dışı yerleşimli, hücre adezyonu, büyümesi, çoğalması, farklılaşması, göçü ve apoptozu kontrol etmek ve aralarındaki ilişkiyi düzenlemek gibi görevleri olan S tipi bir lektin ailesi üyesi olan endojen bir β-galaktozid bağlayıcı proteindir. Bu çalışmada galektin-3 ekspresyonunun metastaz biyolojisindeki rolünü ve kolon karsinomlarında tümör metastazını öngörmedeki rolünü aydınlatmayı amaçladık. Gereç ve Yöntem: Bu çalışmaya normal mukoza-tümör dokusunun geçişini içeren kolon adenokarsinomu bulunan 80 olgu dahil edildi. Bu vakalarda galektin-3 ekspresyonu immünohisto-kimyasal olarak araştırıldı. Bulgular: Galektin-3 ekspresyonu ile yaş, cinsiyet, histolojik tip ve histolojik derece arasında anlamlı bir ilişki olmadığı ancak histolojik derece arttıkça galektin-3 ekspresyon miktarında anlamlı bir artış olduğu görüldü. Komşu normal mukoza ve tümörün galektin-3 ekspresyonu, metastazı olan hastalarda metastazı olmayan hastalara göre anlamlı derecede yüksek bulundu. Vasküler invazyon varlığı ile galektin-3 ekspresyonunun artışı arasında da bir korelasyon tespit edildi. Metastatik odaklardaki galektin-3 ekspresyonunun ortalaması, tümör alanınındakinden daha yüksek bulundu. Bu bulgular metastatik fenotipli hücrelerin daha yüksek miktarda galektin-3 eksprese ettiğini ve galektin-3'ün metastaz patogenezinde henüz yeri belirlenememiş olsa da dolaylı olarak rolü olduğunu düşündürmektedir. Sonuç: Çalışmamızda galektin-3 ekspresyonunun kolon karsinomlarının metastatik sürecinde rol oynayabileceği sonucuna varıldı.
Anahtar Kelimeler:

kolon adenokarsinomları, metastaz, galektin-3

THE ROLE AND IMPORTANCE OF GALECTIN-3 IN COLON CARCINOMA METASTASIS

Objective: Galectin-3 is an endogenous β-galactoside binding protein which is an S-type lectin family member with intracellular and extracellular localization and has certain tasks for controlling cell adhesion, growth, proliferation, differentiation, migration, and apoptosis. In this study we aimed to elucidate the role of galectin-3 expression in metastasis biology and its role in predicting tumor metastasis in colon carcinomas. Materials and Method: In this research, 80 cases with colon adenocarcinoma containing the transition of the normal mucosa-tumor tissue were included. The expression of galectin-3 in these cases was investigated immuno-histochemically. Results: There was no significant relationship between Galectin-3 expression and age, gender, histological type, and histological grade, but there was a significant increase in the amount of galectin-3 expression while the histological grade increased. Galectin-3 expression of the adjacent normal mucosa and tumor was found to be significantly higher in patients with metastases than patients without metastases. There was also a correlation between the presence of vascular invasion and the increase of galectin-3 expression. The mean galectin-3 expression in metastatic foci was higher than that of the tumor area. These findings suggest that the cells with metastatic phenotype express a higher amount of galectin-3 and also galectin-3 has an indirect role in the pathogenesis of metastasis even if its place could not be determined currently. Conclusion: In our study, it was concluded that the expression of galectin-3 may play a role in the metastatic process of colon carcinomas.
Keywords:

colon adenocarcinomas, metastasis, galektin-3,

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  • Sciacchitano S, Lavra L, Morgante A, et.al. Galectin-3: One Molecule for an Alphabet of Diseases, from A to Z. Int J Mol Sci. 2018;26;19(2):379.
  • Hara A, Niwa M, Noguchi K, et. al. Galectin-3 as a Next-Generation Biomarker for Detecting Early Stage of Various Diseases. Biomolecules. 2020 Mar 3;10(3):389.
  • Tuğçe Cay. Immunhistochemical expression of galectin-3 in cancer: a review of the literature. Turk Patoloji Derg. 2012; 28(1):1-10.
  • Boscher C, Zheng YZ, Lakshminarayan R, et. al. Galectin-3 protein regulates mobility of N-cadherin and GM1 ganglioside at cell-cell junctions of mammary carcinoma cells. J Biol Chem. 2012;21;287(39):32940-32952.
  • Yang RY, Liu FT. Galectins in cell growth and apopitosis. Cell Sci. 2003;60(2): 267-276.
  • Funasaka T, Avraham Raz A, Nangia-Makker P. Galectin-3 in angiogenesis and metastasis. Glycobiology. 2014;24(10):886-889.
  • Castells A, Rustgi AK. Chapter 5, Tumor invasion and metastasis, section one, principles of oncogenesis in gastrointestinal cancers. A Companion to Sleisenger & Fordtran's GI and Liver Disease Ed: Rustgi AK. 1st ed. Saunders Published January 2003.
  • Tan K.C.B, Cheung C.-L, Lee A.C.H, Lam J.K.Y, Wong, Y, Shiu S.W.M. Galectin-3 is independently associated with progression of nephropathy in type 2 diabetes mellitus. Diabetologia 2018, 61, 1212–1219.
  • Alam M.L, Katz R, Bellovich K.A, Bhat, Z.Y, Brosius F.C, de Boer I.H, et. al. Soluble ST2 and Galectin-3 and Progression of CKD. Kidney Int. Rep. 2019, 4, 103–111.
  • Gopa D.M, Ayalon N, Wang Y.C, Siwik, D, Sverdlov A, Donohue C, et. al. Galectin-3 is associated with stage B metabolic heart disease and pulmonary hypertension in young obese patients. J. Am. Heart Assoc. 2019, 8, e011100.
  • Clementy N, Garcia B, André C, Bisson A, Benhenda N, Pierre B, et. al. Galectin-3 level predicts response to ablation and outcomes in patients with persistent atrial fibrillation and systolic heart failure. PLoS ONE 2018, 13, e0201517.
  • Andre C, Piver E, Perault R, Bisson A, Pucheux J, Vermes E, et. al. Galectin-3 predicts response and outcomes after cardiac resynchronization therapy 11 Medical and Health Sciences 1102 Cardiorespiratory Medicine and Haematology. J. Transl. Med. 2018, 16, 299.
  • Zuern C.S, Floss N, Mueller I.I, Eick C, Duckheim M, Patzelt J, et. al. Galectin-3 is associated with left ventricular reverse remodeling and outcome after percutaneous mitral valve repair. Int. J. Cardiol. 2018, 263, 104–110.
  • Asleh R, Enriquez-Sarano M, Ja_e A.S, Manemann S.M, Weston S.A, Jiang R, et. al. Galectin-3 Levels and Outcomes After Myocardial Infarction: A Population-Based Study. J. Am. Coll. Cardiol. 2019, 73, 2286–2295.
  • Cui Y, Qi X, Huang A, Li J, Hou W, Liu K. Diferential and Predictive Value of Galectin-3 and Soluble Suppression of Tumorigenicity-2 (sST2) in Heart Failure with Preserved Ejection Fraction. Med. Sci. Monit. 2018, 24, 5139–5146.
  • Dupuy A.M, Kuster N, Curinier C, Huet F, Plawecki M, Solecki K, et al. Exploring collagen remodeling and regulation as prognosis biomarkers in stable heart failure. Clin. Chim. Acta 2019, 490, 167–171.
  • Ghorbani, A, Bhambhani V, Christenson R.H, Meijers W.C, de Boer R.A, Levy, D, et. al. Longitudinal Change in Galectin-3 and Incident Cardiovascular Outcomes. J. Am. Coll. Cardiol. 2018, 72, 3246–3254.
  • Satoh K, Niwa M, Binh N.H, Nakashima M, Kobayashi K, Takamatsu M, et. al. Increase of galectin3 expression in microglia by hyperthermia in delayed neuronal death of hippocampal CA1 following transient forebrain ischemia. Neurosci. Lett. 2011, 504, 199–203.
  • Hisamatsu K, Niwa M, Kobayashi K, Miyazaki T, Hirata A, Hatano Y, et. al. Galectin-3 expression in hippocampal CA2 following transient forebrain ischemia and its inhibition by hypothermia or antiapoptotic agents. Neuroreport 2016, 27, 311–317.
  • Satoh K, Niwa M, Goda W, Binh N.H, Nakashima M, Takamatsu M, et. al. Galectin -3 expression in delayed neuronal death of hippocampal CA1 following transient forebrain ischemia, and its inhibition by hypothermia. Brain Res. 2011, 1382, 266–274.
  • Siew J.J, Chen H.M, Chen H.Y, Chen H.L, Chen C.M, Soong B.W, et. al. Galectin-3 is required for the microglia-mediated brain inflammation in a model of Huntington’s disease. Nat. Commun. 2019, 10, 3473.
  • Ashraf G.M, Baeesa S.S. Investigation of Gal-3 Expression Pattern in Serum and Cerebrospinal Fluid of Patients Su_ering From Neurodegenerative Disorders. Front. Neurosci. 2018, 12, 430.
  • Rotshenker S. The role of Galectin-3/MAC-2 in the activation of the innate-immune function of phagocytosis in microglia in injury and disease. J. Mol. Neurosci. 2009, 39, 99–103.
  • Binh N.H, Satoh K, Kobayashi K, Takamatsu M, Hatano Y, Hirata A, et. al. Galectin-3 in preneoplastic lesions of glioma. J. Neurooncol. 2013, 111, 123–132.
  • Song L, Tang J.W, Owusu L, Sun M.Z, Wu J, Zhang J. Galectin-3 in cancer. Clin. Chim. Acta 2014, 431, 185–191.
  • Fortuna-Costa A, Gomes A.M, Kozlowski E.O, Stelling M.P, Pavão M.S.G. Extracellular galectin3 in tumor progression and metastasis. Front. Oncol. 2014, 4, 138.
  • Funasaka T, Raz A, Nangia-Makker P. Galectin-3 in angiogenesis and metastasis. Glycobiology 2014, 24, 886–891.
  • Xin M, Don X.W, Guo X.L. Role of the interaction between galectin-3 and cell adhesion molecules in cancer metastasis. Biomed. Pharmacother. 2015, 69, 179–185.
  • Ruvolo P.P. Galectin 3 as a guardian of the tumor microenvironment. Biochim. Biophys. Acta Mol. Cell Res. 2016, 1863, 427–437.
  • Zeinali M, Adelinik A, Papian S, Khorramdelazad H, Abedinzadeh M. Role of galectin-3 in the pathogenesis of bladder transitional cell carcinoma. Hum. Immunol. 2015, 76, 770–774.
  • Wang L, Guo X.L. Molecular regulation of galectin-expression and therapeutic implication in cancer progression. Biomed. Pharmacother. 2016, 78, 165–171.
  • Nangia-Makker P, Hogan V, Raz, A. Galectin-3 and cancer stemness. Glycobiology 2018, 28, 172– 181.
  • Wang C, Zhou X, Ma L, Zhuang Y, Wei Y, Zhang L, et. al. Galectin-3 may serve as a marker for poor prognosis in colorectal cancer: A meta-analysis. Pathol. Res. Pract. 2019, 215, 152612.
  • Dimitro C.J. Galectin-binding O-glycosylations as regulators of malignancy. Cancer Res. 2015, 75, 3195–3202.
  • Grioen A.W, Thijssen V.L. Galectins in tumor angiogenesis. Ann. Transl. Med. 2014, 2, 90.
  • Kaltner H, Toegel S, Caballero G.G, Manning J.C, Ledeen R.W, Gabius H.J. Galectins: Their network and roles in immunity/tumor growth control. Histochem. Cell Biol. 2017, 147, 239–256.
  • Dubé-Delarosbil C, St-Pierre Y. The emerging role of galectins in high-fatality cancers. Cell. Mol. Life Sci. 2018, 75, 1215–1226.
  • Wdowiak K, Francuz T, Gallego-Colon E, Ruiz-Agamez N, Kubeczko M, Grochoła I, et. al. Galectin targeted therapy in oncology: Current knowledge and perspectives. Int. J. Mol. Sci. 2018, 19, 210.
  • Chou F.C, Chen H.Y, Kuo C.C, Sytwu H.K. Role of galectins in tumors and in clinical immunotherapy. Int. J. Mol. Sci. 2018, 19, 430.
  • Dings R.P.M, Miller M.C, Grin R.J, Mayo K.H. Galectins as molecular targets for therapeutic intervention. Int. J. Mol. Sci. 2018, 19, 905.
  • Sawa-Wejksza K, Kandefer-Szersze ´ n M. Tumor-Associated Macrophages as Target for Antitumor Therapy. Arch. Immunol. Ther. Exp. 2018, 66, 97–111.
  • Lee C, Jeong H, Bae Y, Shin K, Kang S, Kim H, et. al. Targeting of M2-like tumor-associated macrophages with a melittin-based pro-apoptotic peptide. J. Immunother. Cancer 2019, 7, 1–14
  • Machado C.M.L, Andrade L.N.S, Teixeira V.R, Costa F.F, Melo C.M., dos Santos S.N, et. al. Galectin-3 disruption impaired tumoral angiogenesis by reducing VEGF secretion from TGF 1- induced macrophages. Cancer Med. 2014, 3, 201–214.
  • Irimura T, Matsushita Y, Sutton RC, et al. Increased content of an endogenous lactose binding lectin in human colorecral carcinoma progressed to metastatic stage. Cancer Res. 1991;5: 387-393.
  • Lee EC, Woo HJ, Korzelius CA, Steele GE, Mercurio AM. Carbohydrate-binding protein 35 is the major cell-surface laminin-binding protein in colon carcinoma. Arch Surg. 1991;126: 1496-1502.
  • Schoeppner HL, Raz A, Ho SB, Braselier RS. Expression of an endogenous galactose-binding lectin correlates with neoplastic progression in the colon. cancer 1995;15;75;(12):2818-2826.
  • Lotan R, Ito H, Yasui W, Yokozaki H, Lotan D, Tuhara E. Expression of 31 kDa lactose binding lectin in normal and metastatic gastric carcinomas. Int J Cancer. 1994; 56:474-480.
  • Van Den Brule FA, Berchuck A, Bast RC, Liu FT, Gillet C, Sobel ME, et. al. Differential expression of the 67-Kd laminin receptor and 31-kD human laminin-binding protein human ovarian carcinomas. Eur J Cancer. 1994; 30A: 1096-1099.
  • Lotz MM, Andrews CW, Korzelius CA, et. al. Decreased expression of Mac-2 (carbonhydrate binding protein 35) and loss fo its nuclear localization are associated with the neoplastic progression of colon carcinoma. Proc Natl Acad Sci USA. 1993;90: 3466-3470.
Balıkesir Medical Journal-Cover
  • Yayın Aralığı: Yıllık
  • Başlangıç: 2017
  • Yayıncı: Balıkesir Üniversitesi
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