Galectin-1 and Galectin-3 expression in colon cancer and its correlation with tumor invasion, differentiation, and metastatic spread

Aim. To study the expression of galectin-1 and galectin-3 in colon cancer and the levels of these proteins in the peripheral blood in relation to the differentiation, invasion, and metastatic dissemination.

Materials and Methods. We examined primary tumors and the corresponding peripheral blood samples from 81 patients with colon cancer. Control group consisted of 49 patients with colon adenoma and 17 healthy volunteers. Expression of galectin-1 and galectin-3 in colon tissue was determined by immunohistochemical staining, while their plasma level was measured by enzyme-linked immunosorbent assay. Tumor staging was performed in accordance with the TNM system (AJCC, 2009). Cell differentiation was defined according to the respective clinical guidelines (Russian Cancer Association, 2018).

Results. We detected an elevated expression of galectin-1 and galectin-3 in primary colon cancer as compared with colon adenoma and higher plasma levels of these proteins in colon cancer patients in comparison with healthy volunteers. High expression of tumor and plasma galectin-1 was associated with higher tumor stage (T3/T4) and the presence of local and distant metastases. Overexpression of galectin-3 in the primary tumor correlated with lower differentiation and lymph node metastasis.

Conclusion. Galectin-1 and galectin-3 are involved in colon cancer progression and might be used as predictors of an adverse outcome.

1. Marley AR, Nan H. Epidemiology of colorectal cancer. Int J Mol Epidemiol Genet. 2016;7(3):105-114.

2. Arnold M, Sierra MS, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global patterns and trends in colorectal cancer incidence and mortality. Gut. 2017;66(4):683-691. https://doi.org/10.1136/gutjnl-2015-310912

3. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394-424. https://doi.org/10.3322/caac.21492

4. Fung KY, Nice E, Priebe I, Belobrajdic D, Phatak A, Purins L, Tabor B, Pompeia C, Lockett T, Adams TE, Burgess A, Cosgrove L. Colorectal cancer biomarkers: to be or not to be? Cautionary tales from a road well travelled. World J Gastroenterol. 2014;20(4):888-98. https://doi.org/10.3748/wjg.v20.i4.888

5. Rabinovich GA, Conejo-García JR. Shaping the Immune Landscape in Cancer by Galectin-Driven Regulatory Pathways. J Mol Biol. 2016;428(16):3266-3281. https://doi.org/10.1016/j.jmb.2016.03.021

6. Chou FC, Chen HY, Kuo CC, Sytwu HK. Role of Galectins in Tumors and in Clinical Immunotherapy. Int J Mol Sci. 2018;19(2):430. https://doi.org/10.3390/ijms19020430

7. Orozco CA, Martinez-Bosch N, Guerrero PE, Vinaixa J, Dalotto-Moreno T, Iglesias M, Moreno M, Djurec M, Poirier F, Gabius HJ, Fernandez-Zapico ME, Hwang RF, Guerra C, Rabinovich GA, Navarro P. Targeting galectin-1 inhibits pancreatic cancer progression by modulating tumor-stroma crosstalk. Proc Natl Acad Sci U S A. 2018;115(16):E3769-E3778. https://doi.org/10.1073/pnas.1722434115

8. Dalotto-Moreno T, Croci DO, Cerliani JP, Martinez-Allo VC, Dergan-Dylon S, Méndez-Huergo SP, Stupirski JC, Mazal D, Osinaga E, Toscano MA, Sundblad V, Rabinovich GA, Salatino M. Targeting galectin-1 overcomes breast cancer-associated immunosuppression and prevents metastatic disease. Cancer Res. 2013;73(3):1107-17. https://doi.org/10.1158/0008-5472.CAN-12-2418

9. Méndez-Huergo SP, Blidner AG, Rabinovich GA. Galectins: emerging regulatory checkpoints linking tumor immunity and angiogenesis. Curr Opin Immunol. 2017;45:8-15. https://doi.org/10.1016/j.coi.2016.12.003

10. Ebrahim AH, Alalawi Z, Mirandola L, Rakhshanda R, Dahlbeck S, Nguyen D, Jenkins M, Grizzi F, Cobos E, Figueroa JA, Chiriva-Internati M. Galectins in cancer: carcinogenesis, diagnosis and therapy. Ann Transl Med. 2014;2(9):88. https://doi.org/10.3978/j.issn.2305-5839.2014.09.12

11. Zhao XY, Chen TT, Xia L, Guo M, Xu Y, Yue F, Jiang Y, Chen GQ, Zhao KW. Hypoxia inducible factor-1 mediates expression of galectin-1: the potential role in migration/invasion of colorectal cancer cells. Carcinogenesis. 2010;31(8):1367-75. https://doi.org/10.1093/carcin/bgq116

12. Tang D, Gao J, Wang S, Ye N, Chong Y, Huang Y, Wang J, Li B, Yin W, Wang D. Cancer-associated fibroblasts promote angiogenesis in gastric cancer through galectin-1 expression. Tumour Biol. 2016;37(2):1889-99. https://doi.org/10.1007/s13277-015-3942-9

13. Wu R, Wu T, Wang K, Luo S, Chen Z, Fan M, Xue D, Lu H, Zhuang Q, Xu X. Prognostic significance of galectin-1 expression in patients with cancer: a meta-analysis. Cancer Cell Int. 2018;18:108. https://doi.org/10.1186/s12935-018-0607-y

14. Barrow H, Guo X, Wandall HH, Pedersen JW, Fu B, Zhao Q, Chen C, Rhodes JM, Yu LG. 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(22):7035-46. https://doi.org/10.1158/1078-0432.CCR-11-1462

15. Bacigalupo ML, Carabias P, Troncoso MF. Contribution of galectin-1, a glycan-binding protein, to gastrointestinal tumor progression. World J Gastroenterol. 2017;23(29):5266-5281. https://doi.org/10.3748/wjg.v23.i29.5266

16. Califice S, Castronovo V, Bracke M, van den Brûle F. Dual activities of galectin-3 in human prostate cancer: tumor suppression of nuclear galectin-3 vs tumor promotion of cytoplasmic galectin-3. Oncogene. 2004;23(45):7527-36. https://doi.org/10.1038/sj.onc.1207997

17. Tsuboi K, Shimura T, Masuda N, Ide M, Tsutsumi S, Yamaguchi S, Asao T, Kuwano H. Galectin-3 expression in colorectal cancer: relation to invasion and metastasis. Anticancer Res. 2007;27(4B):2289-2296.

18. Endo K, Kohnoe S, Tsujita E, Watanabe A, Nakashima H, Baba H, Maehara Y. Galectin-3 expression is a potent prognostic marker in colorectal cancer. Anticancer Res. 2005;25(4):3117-3121.

19. Zhao Q, Barclay M, Hilkens J, Guo X, Barrow H, Rhodes JM, Yu LG. Interaction between circulating galectin-3 and cancer-associated MUC1 enhances tumour cell homotypic aggregation and prevents anoikis. Mol Cancer. 2010;9:154. https://doi.org/10.1186/1476-4598-9-154.

20. Zlokachestvennye obrazovaniya obodochnoy kishki i rektosigmoidnogo otdela. Klinicheskie rekomendatsii. 2020. (In Russ). Available at: http://www.oncology.ru/association/clinicalguidelines/2018/rak_obodochnoy_kishki_pr2018.pdf. Accessed: 30 November, 2021.

21. Shimura T, Shibata M, Gonda K, Nakajima T, Chida S, Noda M, Suzuki S, Nakamura I, Ohki S, Takenoshita S. Association between circulating galectin-3 levels and the immunological, inflammatory and nutritional parameters in patients with colorectal cancer. Biomed Rep. 2016;5(2):203-207. https://doi.org/10.3892/br.2016.696

22. Horiguchi N, Arimoto K, Mizutani A, Endo-Ichikawa Y, Nakada H, Taketani S. Galectin-1 induces cell adhesion to the extracellular matrix and apoptosis of non-adherent human colon cancer Colo201 cells. J Biochem. 2003;134(6):869-874.