AKCİĞER KANSERLİ HASTALARDA SERUM GALEKTİN 1 VE 3 DÜZEYLERİNİN, TANISAL VE PROGNOSTİK DEĞERİ

Amaç: Akciğer kanseri kötü prognozlu ve tedavi yanıtı sınırlı olan bir kanser türüdür. Galektinakciğer kanseri patogenezinde rol alabildiği düşünülen fakat akciğer kanseri ile ilişkisinin yeterlidüzeyde gösterilemediği potansiyel bir belirteçtir. Amacımız serumda basit bir yöntem olan galektin1 ve 3 ölçümünün, akciğer kanseri tanısal ya da prognostik belirteci olup olamayacağınıaraştırmaktır.Yöntem: Çalışmaya 49 akciğer kanseri ve 30 sağlıklı kontrol hastası alındı. Serumlarında galektin1 ve 3 düzeyleri galektin ölçüm kiti ile çalışıldı. Akciğer kanserli olgular ve sağlıklı kontrol hastalarıgalektin 1 ve 3’ün tanısal ve prognostik belirteç olup olmayacağı ile ilgili parametreler istatistikselolarak incelendi.Bulgular: Akciğer kanserli hastada galektin 1 ve 3 değeri, kontrol grubuna göre daha düşüktü.Galektin 1 ve 3 düzeyleri ile sağ kalım, evre ve tümör çapı arasında ilişki saptanmazken, metastazve tümör tipi ile negatif ilişkisi saptandı.Sonuç: Galektin 1 ve 3 değeri akciğer kanseri hastalarında sağlıklı olgulara göre daha düşüktürfakat sensitivite ve spesifitesi kısıtlıdır. Literatürde yüksek galektin düzeyi ile akciğer kanseri arasındapozitif saptanan ilişkinin daha geniş hasta gruplarında çalışılmasının uygun olacağı görüşündeyiz.Basit bir tanısal belirteç olarak serum düzeyinin kullanımı umut vaat etmektedir.

Diagnostic and Prognostic Value of Serum Galectin-1 and Galectin-3 Levels in Lung Cancer Patients

Objective: Lung cancer is a cancer type with poor prognosis and limited treatment response. Galectin is a potential marker of lung cancer, which is suggested to be involved in the pathogenesis of lung cancer although its association with lung cancer was not accurately demonstrated. Our aim was to investigate whether the simple method of serum galectin 1 and 3 measurements could be diagnostic or prognostic markers of lung cancer. Methods: Forty-nine lung cancer patients and 30 healthy controls were included in the study. The serum galectin 1 and 3 levels were measured using a Galectin assay kit, provided by contribution of the Hitit University Scientific Research Project (SRP). Lung cancer patients and healthy controls were categorized by galectin 1 and 3 levels, either as high or low, and were evaluated statistically for parameters related to diagnostic and prognostic markers. Results: Galectin 1 and 3 values were lower in lung cancer patients compared to the control group (p= 0.015, p= 0.001, respectively). No significant difference was detected for survival and size of tumor between Galectin 1 and 3 groups. Significant difference was detected for metastasis and type of tumor between Galectin 1 and 3 groups. Conclusion: Galectin 1 and 3 values were lower in lung cancer patients compared to healthy subjects but sensitivity and spesifity were not satisfactory. We believe that, the positive relationship between high galectin levels and lung cancer reported in the literature should be assessed further in larger patient populations. Galectin 1 and 3 were not found associated with survival. Measurement of serum galectin-1 and galectin-3 levels as a diagnostic marker is a simple but promising method.

PDF

___

Iurisci I, Tinari N, Natoli C, Angelucci D, Cianchetti E, Iacobelli S.Concentrations of galectin-3 in the sera of normal controls and cancer patients. Clin Cancer Res 2000;6(4):1389-93
Szoke T, Kayser K, Baumhakel JD, Trojan I, Furak J, et al. Prognostic significance of endogenous adhesion/growth-regulatory lectins in lung cancer. Oncology 2005;69: 167–174
Szoke T, Kayser K, Trojan I, Kayser G, Furak J, et al.. The role of microvascularization and growth/adhesion-regulatory lectins in the prognosis of non-small cell lung cancer in stage II. Eur J Cardiothorac Surg 2007;31: 783–787
van den Brule, F. A., Buicu, C., Berchuck, A., Bast, R. C., Deprez, M., Liu, F. T., Cooper, D. N. W., Pieters, C., Sobel, M., and Castronovo, V. Expression of the 67-kD laminin receptor, galectin-1, and galectin-3 in advanced human uterine adenocarcinoma. Hum Pathol 1996;27: 1185– 1191
Castronovo, V., van den Brule, F. A., Jackers, P., Clausse, N., Liu, F. T., Gillet, C., and Sobel, M. E. Decreased expression of galectin-3 is associated with progression of breast cancer. J Pathol 1996;179: 43–48
Castronovo, V., Campo, E., van den Brule, F., Claysmith, A., Cioce, V., Liu, F. T., Fernandez, P., and Sobel, M. Inverse modulation of steady-state messenger RNA levels of two non-integrin laminin binding proteins in human colon carcinoma. J. Natl. Cancer Inst., 1992;84: 1161–1169
Irimura, T., Matsushita, Y., Sutton, R. C., Carralero, E. D., Ohannesian, D. W., Cleary, K. R., Ota, D. M., Nicolson, G. L., and Lotan, R. Increased content of an endogenous lactose-binding lectin in human colorectal carcinoma progressed to metastatic stages. Cancer Res 1991;51: 387–393
Raz, A., Zhu, D., Hogan, V., Shan, N., Raz, T., Karkash, R., Pazerin, G., and Carmi, P. Evidence for the role of 34 kD galactosidebinding lectin in transformation and metastasis. Int J Cancer 1990;46: 871–877
Raz, A., and Lotan, R. Lectin-like activities associated with human and murine neoplastic cells. Cancer Res 1981;41: 3642–3647
Raz, A., and Lotan, R. Endogenous galactoside-binding lectins: a new class of functional tumor cell surface molecules related to metastasis. Cancer Metastasis Rev 1987;46: 5270–5275
Ochieng, J., Gerold, M., and Raz, A. Dichotomy in the laminin binding properties of soluble and membrane-bound human galactoside binding protein. Biochem Biophys Res Commun 1992;186: 1674–1680
Inohara, H., and Raz, A. Identification of human melanoma cellular and secreted ligands for galectin-3. Biochem Biophys Res Commun 1994;201: 1366–1375
Perillo, N. L., Marcus, M. E., and Baum, L. G. Galectins: versatile modulators of cell adhesion, cell proliferation, and cell death. J Mol Med., 1998;76: 402–412
Moutsatsos, I. K., Wade, M., Schindler, M., and Wang, J. L. Endogenous lectins from cultured cells: nuclear localization of carbohydratebinding protein 35 in proliferating 3T3 fibroblasts. Proc. Natl. Acad. Sci 1987;84: 6452–6456
Sato, S., and Hughes, R. C. J. Regulation of secretion and surface expression of Mac-2, a galactoside-binding protein of macrophages. J. Biol. Chem., 1994;269: 4424–4430
Schulkens IA, Heusschen R, van den Boogaart V, van Suylen RJ, Dingemans AM, Griffioen A et al. Galectin expression profiling identifies galectin-1 and Galectin-9Δ5 as prognostic factors in stage I/II non-small cell lung cancer. PLoS One. 2014;9(9):e107988
Zhou X, Li D, Wang X, Zhang B, Zhu H, Zhao J. Galectin-1 is overexpressed in CD133+ human lung adenocarcinoma cells and promotes their growth and invasiveness. Oncotarget. 2015;6(5):3111- 22.
Pisick E, Jagadeesh S and Salgia R. Receptor tyrosine kinases and inhibitors in lungcancer. ScientificWorldJournal. 2004; 4:589-604.
Kim KW, Moretti L, Mitchell LR, Jung DK and Lu B. Combined Bcl-2/mammalian target of rapamycin inhibition leads to enhanced radiosensitization via induction of apoptosis and autophagy in non-small cell lung tumor xenograft model. Clin Cancer Res. 2009; 15(19):6096- 6105.
Lee MY, Lee SH, Park JH and Han HJ. Interaction of galectin-1 with caveolae induces mouse embryonic stem cell proliferation through the Src, ERas, Akt and mTOR signaling pathways. Cell Mol Life Sci. 2009; 66(8):1467- 1478.
Kuo PL, Hung JY, Huang SK, Chou SH, Cheng DE, Jong YJ, Hung CH, Yang CJ, Tsai YM, Hsu YL and Huang MS. Lung cancer-derived galectin-1 mediates dendritic cell anergy through inhibitor of DNA binding 3/IL-10 signaling pathway. J Immunol. 2011; 186(3):1521- 1530.
Chung LY, Tang SJ, Sun GH, Chou TY, Yeh TS, Yu SL and Sun KH. Galectin-1 promotes lung cancer progression and chemoresistance by upregulating p38 MAPK, ERK, and cyclooxygenase-2. Clin Cancer Res. 2012; 18(15):4037- 4047.
Jung EJ, Moon HG, Cho BI, Jeong CY, Joo YT, Lee YJ, et al. Galectin-1 expressionin cancer-associated stromal cells correlates tumor invasiveness and tumorprogression in breast cancer. Int J Cancer 2007;120(11):2331–8.
Hsu YL, Wu CY, Hung JY, Lin YS, Huang MS, Kuo PL. Galectin-1 promoteslung cancer tumor metastasis by potentiating integrin alpha6beta4 andNotch1/Jagged2 signaling pathway. Carcinogenesis 2013;34(6):1370–81.
Wu MH, Hong TM, Cheng HW, Pan SH, Liang YR, Hong HC, et al.Galectin-1-mediated tumor invasion and metastasis, up-regulated matrix met-alloproteinase expression, and reorganized actin cytoskeletons. Mol Cancer Res 2009;7(3):311–8.
Paz A, Haklai R, Elad-Sfadia G, Ballan E, Kloog Y. Galectin-1 binds oncogenic H-Ras to mediate Ras membrane anchorage and cell transformation. Oncogene 2001;20(51):7486–93.
Rabinovich GA, Toscano MA. Turning ‘sweet’ on immunity: galectin–glycaninteractions in immune tolerance and inflammation. Nat Rev Immunol 2009;9(5):338–52.
Chung LY, Tang SJ, Sun GH, Chou TY, Yeh TS, Yu SL, et al. Galectin-1 promoteslung cancer progression and chemoresistance by upregulating p38 MAPK, ERK,and cyclooxygenase-2. Clin Cancer Res 2012;18(15):4037–47.
Carlini MJ, Roitman P, Nuñez M, Pallotta MG, Boggio G, Smith D et al. Clinical relevance of galectin-1 expression in non-small cell lung cancer patients. Lung Cancer. 2014;84(1):73-8
Szöke T, Kayser K, Kayser G, Furak J, Tiszlavicz L, Baumhäkel JD, et al. Therole of microvascularization and growth/adhesion-regulatory lectins in theprognosis of non-small cell lung cancer in stage II. Eur J Cardiothorac Surg 2007;31(5):783–7.
Szöke T, Kayser K, Baumhakel JD, Trojan I, Furak J, Tiszlavicz L, et al. Prognosticsignificance of endogenous adhesion/growth-regulatory lectins in lung cancer.Oncology 2005;69(2):167–74.
Banh A, Zhang J, Cao H, Bouley DM, Kwok S, Kong C, et al. Tumor galectin-1mediates tumor growth and metastasis through regulation of T-cell apoptosis.Cancer Res 2011;71(13):4423–31.
Kuo PL, Huang MS, Cheng DE, Hung JY, Yang CJ, Chou SH. Lung cancer-derived galectin-1 enhances tumorigenic potentiation of tumor-associateddendritic cells by expressing heparin-binding EGFlike growth factor. J BiolChem 2012;287(13):9753–64.
Rubinstein N, Alvarez M, Zwirner NW, Toscano MA, Ilarregui JM, Bravo A,et al. Targeted inhibition of galectin-1 gene expression in tumor cells resultsin heightened T cell-mediated rejection; a potential mechanism of tumor-immune privilege. Cancer Cell 2004;5(3):241–51.
Schulkens IA, Heusschen R, van den Boogaart V, van Suylen RJ, Dingemans AM, et al. Galectin expression profiling identifies galectin-1 and Galectin-9Δ5 as prognostic factors in stage I/II non-small cell lung cancer. PLoS One. 2014:26;9(9):e107988.
Carlinia MJ, Roitmanb P, Nu˜nezb M, Pallottab MG, Boggiob G, Smithb D, Salatinoc M, Kier Jofféa ED, Rabinovich GA, Puricelli LI. Clinical relevance of galectin-1 expression in non-smallcell lung cancer patients. Lung Cancer 2014; 84: 73–78.
Astorgues-Xerri L, Riveiro M.E, Tijeras-Raballand A, Serova M, Neuzillet C, Albert S, Raymond E, Faivre S. Unraveling galectin-1 as a novel therapeutic target for cancer. Cancer Treatment Reviews 2014; 40: 307–319.
Croci DO, Cerliani JP, Dalotto-Moreno T, Me´ndez-Huergo SP, Mascanfroni ID, et al. Glycosylation-Dependent Lectin-Receptor Interactions Preserve Angiogenesis in Anti-VEGF Refractory Tumors. Cell 2014;156: 744–758.
Cardenas Delgado VM, Nugnes LG, Colombo LL, Troncoso MF, Fernandez MM, et al. Modulation of endothelial cell migration and angiogenesis: a novel function for the ‘‘tandem-repeat’’ lectin galectin-8. FASEB J 2011;25: 242–254.
Nobumoto A, Nagahara K, Oomizu S, Katoh S, Nishi N, et al. Galectin- 9 suppresses tumor metastasis by blocking adhesion to endothelium and extracellular matrices. Glycobiology 2008;18: 735–744.
Dalotto-Moreno T, Croci DO, Cerliani JP, Martinez-Allo VC, Dergan-Dylon S, et al. Targeting galectin-1 overcomes breast cancerassociated immunosuppression and prevents metastatic disease. Cancer Res 2013;73: 1107–1117.
Barrow H, Guo X, Wandall HH, Pedersen JW, Fu B, et al. Serum galectin-2, -4, and -8 are greatly increased in colon and breast cancer patients and promote cancer cell adhesion to blood vascular endothelium. Clin Cancer Res 2011;17: 7035–7046.
Rabinovich GA, Croci DO. Regulatory circuits mediated by lectinglycan interactions in autoimmunity and cancer. Immunity 2012;36: 322–335.
Yang RY, Rabinovich GA, Liu FT. Galectins: structure, function and therapeutic potential. Expert reviews in molecular medicine 2008;13;10:e17.
Thijssen VL, Rabinovich GA, Griffioen AW. Vascular galectins: regulators of tumor progression and targets for cancer therapy. Cytokine Growth Factor Rev 2013;24: 547–558.
Barondes SH, Castronovo V, Cooper DN, Cummings RD, Drickamer K, et al. Galectins: a family of animal beta-galactoside-binding lectins. Cell 1994;76: 597–598.
Goldstraw P, Crowley J, Chansky K, Giroux DJ, Groome PA, RamiPortaR, et al. The IASLC Lung Cancer Staging Project: proposals for the revision of the TNM stage groupings in the forthcoming (seventh) edition ofthe TNM Classification of malignant tumours. J Thorac Oncol 2007;2(8):706–14.
Collins LG, Haines C, Perkel R, Enck RE. Lung cancer: diagnosis and management. Am Fam Physician 2007;75(1):56–63.