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The expression of galectin-3 in breast cancer and its association with chemoresistance: a systematic review of the literature

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Abstract

Purpose

Galectin-3 is a Mr 31,000 protein that belongs to a family of carbohydrate-binding proteins. Galectin-3 has already been associated with protection against apoptosis through cell to cell or cell to matrix adhesion processes. It seems that galectin-3 plays an important role in tumor progression, cell growth, invasion and metastasis. Galectin-3 is the only member of the chimeric galectins that has an N-terminal glycine and proline domain and a C-terminal carbohydrate recognition domain that allows galectin-3 to accommodate larger structures such us polylactosaminoglycans and intervene to DNA damage repair process. In this systematic review, our primary goal is to identify the effect of galectin-3 expression in association with drug resistance and apoptosis inhibition in breast cancer.

Materials and methods

Scopus and PubMed databases were searched on 26 November 2018 using the following combination of keywords: (galectin-3 OR gal-3 OR LGALS3) AND (breast cancer) AND (chemoresistance OR (drug resistance) OR chemosensitivity). All the articles in English, regardless the time of publication, text availability and species included were initially accepted.

Results

In the majority of the included studies, the expression of galectin-3 had a protective role in cell survival via different pathways such as the response to DNA damage and repair or the inhibition of apoptosis after treatment with a chemotherapeutic agent.

Conclusion

Galectin-3 expression in breast tumors might be an important factor in the selection of the most suitable treatment.

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References

  1. Liu FT, Rabinovich GA (2005) Galectins as modulators of tumour progression. Nat Rev Cancer 5(1):29–41

    CAS  PubMed  Google Scholar 

  2. Barondes SH, Castronovo V, Cooper DN, Cummings RD, Drickamer K, Feizi T et al (1994) Galectins: a family of animal beta-galactoside-binding lectins. Cell 76(4):597–598

    CAS  PubMed  Google Scholar 

  3. Takenaka Y, Fukumori T, Raz A (2002) Galectin-3 and metastasis. Glycoconj J 19(7–9):543–549

    CAS  PubMed  Google Scholar 

  4. Yang RY, Liu FT (2003) Galectins in cell growth and apoptosis. Cell Mol Life Sci 60(2):267–276

    CAS  PubMed  Google Scholar 

  5. Kim HR, Lin HM, Biliran H, Raz A (1999) Cell cycle arrest and inhibition of anoikis by galectin-3 in human breast epithelial cells. Cancer Res 59(16):4148–4154

    CAS  PubMed  Google Scholar 

  6. Akahani S, Nangia-Makker P, Inohara H, Kim HR, Raz A (1997) Galectin-3: a novel antiapoptotic molecule with a functional BH1 (NWGR) domain of Bcl-2 family. Cancer Res 57(23):5272–5276

    CAS  PubMed  Google Scholar 

  7. Hughes RC (2001) Galectins as modulators of cell adhesion. Biochimie 83(7):667–676

    CAS  PubMed  Google Scholar 

  8. Lord CJ, Ashworth A (2012) The DNA damage response and cancer therapy. Nature 481(7381):287–294

    CAS  PubMed  Google Scholar 

  9. Knibbs RN, Agrwal N, Wang JL, Goldstein IJ (1993) Carbohydrate-binding protein 35. II. Analysis of the interaction of the recombinant polypeptide with saccharides. J Biol Chem 268(20):14940–14947

    CAS  PubMed  Google Scholar 

  10. Dumic J, Dabelic S, Flogel M (2006) Galectin-3: an open-ended story. Biochim Biophys Acta 1760(4):616–635

    CAS  PubMed  Google Scholar 

  11. Gillenwater A, Xu XC, el-Naggar AK, Clayman GL, Lotan R (1996) Expression of galectins in head and neck squamous cell carcinoma. Head Neck 18(5):422–432

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  13. Turkoz HK, Oksuz H, Yurdakul Z, Ozcan D (2008) Galectin-3 expression in tumor progression and metastasis of papillary thyroid carcinoma. Endocr Pathol 19(2):92–96

    PubMed  Google Scholar 

  14. Kim SJ, Shin JY, Cheong TC, Choi IJ, Lee YS, Park SH et al (2011) Galectin-3 germline variant at position 191 enhances nuclear accumulation and activation of beta-catenin in gastric cancer. Clin Exp Metastasis 28(8):743–750

    CAS  PubMed  Google Scholar 

  15. Chen YR, Juan HF, Huang HC, Huang HH, Lee YJ, Liao MY et al (2006) Quantitative proteomic and genomic profiling reveals metastasis-related protein expression patterns in gastric cancer cells. J Proteome Res 5(10):2727–2742

    CAS  PubMed  Google Scholar 

  16. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A (2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 68:394–424

    Google Scholar 

  17. Honjo Y, Nangia-Makker P, Inohara H, Raz A (2001) Down-regulation of galectin-3 suppresses tumorigenicity of human breast carcinoma cells. Clin Cancer Res 7(3):661–668

    CAS  PubMed  Google Scholar 

  18. Song YK, Billiar TR, Lee YJ (2002) Role of galectin-3 in breast cancer metastasis: involvement of nitric oxide. Am J Pathol 160(3):1069–1075

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Cory S, Adams JM (2002) The Bcl2 family: regulators of the cellular life-or-death switch. Nat Rev Cancer 2(9):647–656

    CAS  PubMed  Google Scholar 

  20. Boya P, Morales MC, Gonzalez-Polo RA, Andreau K, Gourdier I, Perfettini JL et al (2003) The chemopreventive agent N-(4-hydroxyphenyl)retinamide induces apoptosis through a mitochondrial pathway regulated by proteins from the Bcl-2 family. Oncogene 22(40):6220–6230

    CAS  PubMed  Google Scholar 

  21. Moon BK, Lee YJ, Battle P, Jessup JM, Raz A, Kim HR (2001) Galectin-3 protects human breast carcinoma cells against nitric oxide-induced apoptosis: implication of galectin-3 function during metastasis. Am J Pathol 159(3):1055–1060

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Koo JS, Jung W (2011) Clinicopathlogic and immunohistochemical characteristics of triple negative invasive lobular carcinoma. Yonsei Med J 52(1):89–97

    PubMed  Google Scholar 

  23. Cheong TC, Shin JY, Chun KH (2010) Silencing of galectin-3 changes the gene expression and augments the sensitivity of gastric cancer cells to chemotherapeutic agents. Cancer Sci 101(1):94–102

    CAS  PubMed  Google Scholar 

  24. Mazurek N, Byrd JC, Sun Y, Ueno S, Bresalier RS (2011) A galectin-3 sequence polymorphism confers TRAIL sensitivity to human breast cancer cells. Cancer 117(19):4375–4380

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Zhang H, Luo M, Liang X, Wang D, Gu X, Duan C et al (2014) Galectin-3 as a marker and potential therapeutic target in breast cancer. PLoS ONE 9(9):e103482

    PubMed  PubMed Central  Google Scholar 

  26. Carvalho RS, Fernandes VC, Nepomuceno TC, Rodrigues DC, Woods NT, Suarez-Kurtz G et al (2014) Characterization of LGALS3 (galectin-3) as a player in DNA damage response. Cancer Biol Ther 15(7):840–850

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Choi JH, Chun KH, Raz A, Lotan R (2004) Inhibition of N-(4-hydroxyphenyl)retinamide-induced apoptosis in breast cancer cells by galectin-3. Cancer Biol Ther 3(5):447–452

    CAS  PubMed  Google Scholar 

  28. Wang Y, Nangia-Makker P, Balan V, Hogan V, Raz A (2010) Calpain activation through galectin-3 inhibition sensitizes prostate cancer cells to cisplatin treatment. Cell Death Dis 1:e101

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Oishi T, Itamochi H, Kigawa J, Kanamori Y, Shimada M, Takahashi M et al (2007) Galectin-3 may contribute to Cisplatin resistance in clear cell carcinoma of the ovary. Int J Gynecol Cancer 17(5):1040–1046

    CAS  PubMed  Google Scholar 

  30. Mazurek N, Sun YJ, Liu KF, Gilcrease MZ, Schober W, Nangia-Makker P et al (2007) Phosphorylated galectin-3 mediates tumor necrosis factor-related apoptosis-inducing ligand signaling by regulating phosphatase and tensin homologue deleted on chromosome 10 in human breast carcinoma cells. J Biol Chem 282(29):21337–21348

    CAS  PubMed  Google Scholar 

  31. Balan V, Nangia-Makker P, Schwartz AG, Jung YS, Tait L, Hogan V et al (2008) Racial disparity in breast cancer and functional germ line mutation in galectin-3 (rs4644): a pilot study. Cancer Res 68(24):10045–10050

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Ashkenazi A, Dixit VM (1998) Death receptors: signaling and modulation. Science 281(5381):1305–1308

    CAS  Google Scholar 

  33. Cretney E, Takeda K, Smyth MJ (2007) Cancer: novel therapeutic strategies that exploit the TNF-related apoptosis-inducing ligand (TRAIL)/TRAIL receptor pathway. Int J Biochem Cell Biol 39(2):280–286

    CAS  PubMed  Google Scholar 

  34. Baj G, Arnulfo A, Deaglio S, Mallone R, Vigone A, De Cesaris MG et al (2002) Arsenic trioxide and breast cancer: analysis of the apoptotic, differentiative and immunomodulatory effects. Breast Cancer Res Treat 73(1):61–73

    CAS  PubMed  Google Scholar 

  35. Lo-Coco F, Avvisati G, Vignetti M, Thiede C, Orlando SM, Iacobelli S et al (2013) Retinoic acid and arsenic trioxide for acute promyelocytic leukemia. N Engl J Med 369(2):111–121

    CAS  PubMed  Google Scholar 

  36. Dilda PJ, Hogg PJ (2007) Arsenical-based cancer drugs. Cancer Treat Rev 33(6):542–564

    CAS  PubMed  Google Scholar 

  37. Chen Z, Chen GQ, Shen ZX, Sun GL, Tong JH, Wang ZY et al (2002) Expanding the use of arsenic trioxide: leukemias and beyond. Semin Hematol 39(2 Suppl 1):22–26

    CAS  PubMed  Google Scholar 

  38. Berenson JR, Yeh HS (2006) Arsenic compounds in the treatment of multiple myeloma: a new role for a historical remedy. Clin Lymphoma Myeloma 7(3):192–198

    CAS  PubMed  Google Scholar 

  39. Poehlmann A, Roessner A (2010) Importance of DNA damage checkpoints in the pathogenesis of human cancers. Pathol Res Pract 206(9):591–601

    CAS  PubMed  Google Scholar 

  40. Yarden RI, Pardo-Reoyo S, Sgagias M, Cowan KH, Brody LC (2002) BRCA1 regulates the G2/M checkpoint by activating Chk1 kinase upon DNA damage. Nat Genet 30(3):285–289

    PubMed  Google Scholar 

  41. Tembe V, Henderson BR (2007) BARD1 translocation to mitochondria correlates with Bax oligomerization, loss of mitochondrial membrane potential, and apoptosis. J Biol Chem 282(28):20513–20522

    CAS  PubMed  Google Scholar 

  42. Yu F, Finley RL Jr, Raz A, Kim HR (2002) Galectin-3 translocates to the perinuclear membranes and inhibits cytochrome c release from the mitochondria. A role for synexin in galectin-3 translocation. J Biol Chem 277(18):15819–15827

    CAS  PubMed  Google Scholar 

  43. Oridate N, Lotan D, Xu XC, Hong WK, Lotan R (1996) Differential induction of apoptosis by all-trans-retinoic acid and N-(4-hydroxyphenyl) retinamide in human head and neck squamous cell carcinoma cell lines. Clin Cancer Res 2(5):855–863

    CAS  PubMed  Google Scholar 

  44. Zou CP, Kurie JM, Lotan D, Zou CC, Hong WK, Lotan R (1998) Higher potency of N-(4-hydroxyphenyl) retinamide than all-trans-retinoic acid in induction of apoptosis in non-small cell lung cancer cell lines. Clin Cancer Res 4(5):1345–1355

    CAS  PubMed  Google Scholar 

  45. Zou C, Liebert M, Zou C, Grossman HB, Lotan R (2001) Identification of effective retinoids for inhibiting growth and inducing apoptosis in bladder cancer cells. J Urol 165(3):986–992

    CAS  PubMed  Google Scholar 

  46. Maurer BJ, Metelitsa LS, Seeger RC, Cabot MC, Reynolds CP (1999) Increase of ceramide and induction of mixed apoptosis/necrosis by N-(4-hydroxyphenyl)—retinamide in neuroblastoma cell lines. J Natl Cancer Inst 91(13):1138–1146

    CAS  PubMed  Google Scholar 

  47. Sun SY, Yue P, Lotan R (1999) Induction of apoptosis by N-(4-hydroxyphenyl) retinamide and its association with reactive oxygen species, nuclear retinoic acid receptors, and apoptosis-related genes in human prostate carcinoma cells. Mol Pharmacol 55(3):403–410

    CAS  PubMed  Google Scholar 

  48. Delia D, Aiello A, Lombardi L, Pelicci PG, Grignani F, Grignani F et al (1993) N-(4-hydroxyphenyl) retinamide induces apoptosis of malignant hemopoietic cell lines including those unresponsive to retinoic acid. Cancer Res 53(24):6036–6041

    CAS  PubMed  Google Scholar 

  49. De Palo G, Mariani L, Camerini T, Marubini E, Formelli F, Pasini B et al (2002) Effect of fenretinide on ovarian carcinoma occurrence. Gynecol Oncol 86(1):24–27

    PubMed  Google Scholar 

  50. Wang TT, Phang JM (1996) Effect of N-(4-hydroxyphenyl) retinamide on apoptosis in human breast cancer cells. Cancer Lett 107(1):65–71

    CAS  PubMed  Google Scholar 

  51. Matarrese P, Tinari N, Semeraro ML, Natoli C, Iacobelli S, Malorni W (2000) Galectin-3 overexpression protects from cell damage and death by influencing mitochondrial homeostasis. FEBS Lett 473(3):311–315

    CAS  PubMed  Google Scholar 

  52. Zhou LJ, Zhu XZ (2000) Reactive oxygen species-induced apoptosis in PC12 cells and protective effect of bilobalide. J Pharmacol Exp Ther 293(3):982–988

    CAS  PubMed  Google Scholar 

  53. Lu HF, Hsueh SC, Ho YT, Kao MC, Yang JS, Chiu TH et al (2007) ROS mediates baicalin-induced apoptosis in human promyelocytic leukemia HL-60 cells through the expression of the Gadd153 and mitochondrial-dependent pathway. Anticancer Res 27(1A):117–125

    CAS  PubMed  Google Scholar 

  54. Hail N Jr, Lotan R (2001) Mitochondrial respiration is uniquely associated with the prooxidant and apoptotic effects of N-(4-hydroxyphenyl) retinamide. J Biol Chem 276(49):45614–45621

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Third Department of Obstetrics and Gynecology, Attikon University Hospital, Medical School of the National and Kapodistrian University of Athens, Athens, Greece

    Ioannis Boutas, Anastasios Potiris & Sophia Kalantaridou

  2. Department of Obstetrics and Women’s Health, University Medical Center, Johannes Gutenberg-University, Mainz, Germany

    Ioannis Boutas, Walburgis Brenner, Antje Lebrecht, Annette Hasenburg & Marcus Schmidt

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  1. Ioannis Boutas
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  2. Anastasios Potiris
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  3. Walburgis Brenner
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  4. Antje Lebrecht
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  5. Annette Hasenburg
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  6. Sophia Kalantaridou
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  7. Marcus Schmidt
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Contributions

IB: data collection and manuscript writing; AP: data collection and manuscript writing; WB: data management; AL: data management; AH: data review and manuscript editing; SK: data review and manuscript editing; and MS: project development and manuscript editing.

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Correspondence to Anastasios Potiris.

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Boutas, I., Potiris, A., Brenner, W. et al. The expression of galectin-3 in breast cancer and its association with chemoresistance: a systematic review of the literature. Arch Gynecol Obstet 300, 1113–1120 (2019). https://doi.org/10.1007/s00404-019-05292-9

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  • DOI: https://doi.org/10.1007/s00404-019-05292-9

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