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Galectins in prostate and bladder cancer: tumorigenic roles and clinical opportunities

Nature Reviews Urology volume 16, pages 433–445 (2019)Cite this article

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Abstract

Advanced prostate and bladder cancer are two outstanding unmet medical needs for urological oncologists. The high prevalence of these tumours, lack of effective biomarkers and limited effective treatment options highlight the importance of basic research in these diseases. Galectins are a family of β-galactoside-binding proteins that are frequently altered (upregulated or downregulated) in a wide range of tumours and have roles in different stages of tumour development and progression, including immune evasion. In particular, altered expression levels of different members of the galectin family have been reported in prostate and bladder cancers, which, together with the aberrant glycosylation patterns found in tumour cells and the constituent cell types of the tumour microenvironment, can result in malignant transformation and tumour progression. Understanding the roles of galectin family proteins in the development and progression of prostate and bladder cancer could yield key insights to inform the clinical management of these diseases.

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Fig. 1: Classification of the mammalian galectins.
Fig. 2: Roles of galectins in prostate and bladder tumour development and progression.

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References

  1. Siegel, R. L., Miller, K. D. & Jemal, A. Cancer statistics, 2018. CA Cancer J. Clin. 68, 7–30 (2018).

    PubMed  Google Scholar 

  2. Risbridger, G. P., Toivanen, R. & Taylor, R. A. Preclinical models of prostate cancer: patient-derived xenografts, organoids, and other explant models. Cold Spring Harb. Perspect. Med. 8, a030536 (2018).

    PubMed  PubMed Central  Google Scholar 

  3. Fizazi, K. et al. Abiraterone plus prednisone in metastatic, castration-sensitive prostate cancer. N. Engl. J. Med. 377, 352–360 (2017).

    CAS  PubMed  Google Scholar 

  4. James, N. D. et al. Abiraterone for prostate cancer not previously treated with hormone therapy. N. Engl. J. Med. 377, 338–351 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Shipley, W. U. et al. Radiation with or without antiandrogen therapy in recurrent prostate cancer. N. Engl. J. Med. 376, 417–428 (2017).

    PubMed  PubMed Central  Google Scholar 

  6. Sathianathen, N. J., Konety, B. R., Crook, J., Saad, F. & Lawrentschuk, N. Landmarks in prostate cancer. Nat. Rev. Urol. 15, 627–642 (2018).

    PubMed  Google Scholar 

  7. Cotter, K. A. & Rubin, M. A. Sequence of events in prostate cancer. Nature 560, 557–559 (2018).

    CAS  PubMed  Google Scholar 

  8. Arriaga, J. M. & Abate-Shen, C. Genetically engineered mouse models of prostate cancer in the postgenomic era. Cold Spring Harb. Perspect. Med. 9, a030528 (2019).

    PubMed  PubMed Central  Google Scholar 

  9. van der Toom, E. E. et al. Prostate-specific markers to identify rare prostate cancer cells in liquid biopsies. Nat. Rev. Urol. 16, 7–22 (2019).

    PubMed  PubMed Central  Google Scholar 

  10. Sved, P. D., Gomez, P., Manoharan, M., Kim, S. S. & Soloway, M. S. Limitations of biopsy Gleason grade: implications for counseling patients with biopsy Gleason score 6 prostate cancer. J. Urol. 172, 98–102 (2004).

    PubMed  Google Scholar 

  11. Cohen, M. S. et al. Comparing the Gleason Prostate Biopsy and Gleason Prostatectomy Grading System: The Lahey Clinic Medical Center experience and an international meta-analysis. Eur. Urol. 54, 371–381 (2008).

    PubMed  Google Scholar 

  12. Baciarello, G., Gizzi, M. & Fizazi, K. Advancing therapies in metastatic castration-resistant prostate cancer. Expert Opin. Pharmacother. 19, 1797–1804 (2018).

    CAS  PubMed  Google Scholar 

  13. Xu, J. X. et al. FDA approval summary: nivolumab in advanced renal cell carcinoma after anti-angiogenic therapy and exploratory predictive biomarker analysis. Oncologist 22, 311–317 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Powles, T. et al. Updated European Association of Urology Guidelines recommendations for the treatment of first-line metastatic clear cell renal cancer. Eur. Urol. 73, 311–315 (2017).

    PubMed  Google Scholar 

  15. Bellmunt, J. et al. Pembrolizumab as second-line therapy for advanced urothelial carcinoma. N. Engl. J. Med. 376, 1015–1026 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Balar, A. V. et al. First-line pembrolizumab in cisplatin-ineligible patients with locally advanced and unresectable or metastatic urothelial cancer (KEYNOTE-052): a multicentre, single-arm, phase 2 study. Lancet Oncol. 18, 1483–1492 (2017).

    CAS  PubMed  Google Scholar 

  17. Siefker-Radtke, A. & Curti, B. Immunotherapy in metastatic urothelial carcinoma: focus on immune checkpoint inhibition. Nat. Rev. Urol. 15, 112–124 (2017).

    PubMed  Google Scholar 

  18. Carlo, M. I., Voss, M. H. & Motzer, R. J. Checkpoint inhibitors and other novel immunotherapies for advanced renal cell carcinoma. Nat. Rev. Urol. 13, 420–431 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Maia, M. C. & Hansen, A. R. A comprehensive review of immunotherapies in prostate cancer. Crit. Rev. Oncol. Hematol. 113, 292–303 (2017).

    PubMed  Google Scholar 

  20. Matsumoto, K. et al. Late recurrence and progression in non-muscle–invasive bladder cancers after 5-year tumor-free periods. Urology 75, 1385–1390 (2010).

    PubMed  Google Scholar 

  21. Tabayoyong, W. B. et al. Systematic review on the utilization of maintenance intravesical chemotherapy in the management of non-muscle-invasive bladder cancer. Eur. Urol. Focus 4, 512–521 (2018).

    Google Scholar 

  22. Türkölmez, K., Tokgöz, H., Reşorlu, B., Köse, K. & Bedük, Y. Muscle-invasive bladder cancer: predictive factors and prognostic difference between primary and progressive tumors. Urology 70, 477–481 (2007).

    PubMed  Google Scholar 

  23. Marcq, G. et al. Contemporary best practice in the use of neoadjuvant chemotherapy in muscle-invasive bladder cancer. Ther. Adv. Urol. 11, 175628721882367 (2019).

    Google Scholar 

  24. Rodriguez-Vida, A., Perez-Gracia, J. L. & Bellmunt, J. Immunotherapy combinations and sequences in urothelial cancer: facts and hopes. Clin. Cancer Res. 24, 6115–6124 (2018).

    PubMed  Google Scholar 

  25. Anastasiadis, A. & de Reijke, T. M. Best practice in the treatment of nonmuscle invasive bladder cancer. Ther. Adv. Urol. 4, 13–32 (2012).

    PubMed  PubMed Central  Google Scholar 

  26. Canesin, G. et al. Galectin-3 expression is associated with bladder cancer progression and clinical outcome. Tumour Biol. 31, 277–285 (2010).

    CAS  PubMed  Google Scholar 

  27. Sakaki, M. et al. Serum level of galectin-3 in human bladder cancer. J. Med. Invest. 55, 127–132 (2008).

    PubMed  Google Scholar 

  28. Balan, V. et al. Galectin-3: a possible complementary marker to the PSA blood test. Onco_target 4, 542–549 (2013).

    PubMed  PubMed Central  Google Scholar 

  29. Wang, Y. et al. The significance of galectin-3 as a new basal cell marker in prostate cancer. Cell Death Dis. 4, e753 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Ahmed, H., Cappello, F., Rodolico, V. & Vasta, G. R. Evidence of heavy methylation in the galectin 3 promoter in early stages of prostate adenocarcinoma: development and validation of a methylated marker for early diagnosis of prostate cancer. Transl Oncol. 2, 146–156 (2009).

    PubMed  PubMed Central  Google Scholar 

  31. Wu, T.-F. et al. Galectin-1 dysregulation independently predicts disease specific survival in bladder urothelial carcinoma. J. Urol. 193, 1002–1008 (2015).

    CAS  PubMed  Google Scholar 

  32. Kramer, M. W. et al. Decreased expression of galectin-3 predicts tumour recurrence in pTa bladder cancer. Oncol. Rep. 20, 1403–1408 (2008).

    PubMed  Google Scholar 

  33. Langbein, S. et al. Gene-expression signature of adhesion/growth-regulatory tissue lectins (galectins) in transitional cell cancer and its prognostic relevance. Histopathology 51, 681–690 (2007).

    CAS  PubMed  Google Scholar 

  34. Wu, M.-M. et al. Promoter hypermethylation of LGALS4 correlates with poor prognosis in patients with urothelial carcinoma. Onco_target 8, 23787–23802 (2017).

    PubMed  PubMed Central  Google Scholar 

  35. Liu, Y. et al. Galectin-9 as a prognostic and predictive biomarker in bladder urothelial carcinoma. Urol. Oncol. 35, 349–355 (2017).

    CAS  PubMed  Google Scholar 

  36. Cummings, R. D., Liu, F.-T. & Vasta, G. R. in Essentials of Glycobiology [Internet] 3rd edn Ch. 36 (eds Varki, A. et al.) (Cold Spring Harbor Laboratory Press, 2017).

  37. Tsai, C.-M. et al. Galectin-1 and galectin-8 have redundant roles in promoting plasma cell formation. J. Immunol. 187, 1643–1652 (2011).

    CAS  PubMed  Google Scholar 

  38. Tribulatti, M. V., Figini, M. G., Carabelli, J., Cattaneo, V. & Campetella, O. Redundant and antagonistic functions of galectin-1, -3, and -8 in the elicitation of T cell responses. J. Immunol. 188, 2991–2999 (2012).

    CAS  PubMed  Google Scholar 

  39. Vyakarnam, A., Dagher, S. F., Wang, J. L. & Patterson, R. J. Evidence for a role for galectin-1 in pre-mRNA splicing. Mol. Cell. Biol. 17, 4730–4737 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Munkley, J., Mills, I. G. & Elliott, D. J. The role of glycans in the development and progression of prostate cancer. Nat. Rev. Urol. 13, 324–333 (2016).

    CAS  PubMed  Google Scholar 

  41. Ohyama, C. Glycosylation in bladder cancer. Int. J. Clin. Oncol. 13, 308–313 (2008).

    CAS  PubMed  Google Scholar 

  42. Stowell, S. R., Ju, T. & Cummings, R. D. Protein glycosylation in cancer. Annu. Rev. Pathol. 10, 473–510 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Pinho, S. S. & Reis, C. A. Glycosylation in cancer: mechanisms and clinical implications. Nat. Rev. Cancer 15, 540–555 (2015).

    CAS  PubMed  Google Scholar 

  44. Rabinovich, G. A. & Croci, D. O. Regulatory circuits mediated by lectin-glycan interactions in autoimmunity and cancer. Immunity 36, 322–335 (2012).

    CAS  PubMed  Google Scholar 

  45. Croci, D. O. et al. Glycosylation-dependent lectin-receptor interactions preserve angiogenesis in anti-VEGF refractory tumors. Cell 156, 744–758 (2014).

    CAS  PubMed  Google Scholar 

  46. Kasbaoui, L., Harb, J., Bernard, S. & Meflah, K. Differences in glycosylation state of fibronectin from two rat colon carcinoma cell lines in relation to tumoral progressiveness. Cancer Res. 49, 5317–5322 (1989).

    CAS  PubMed  Google Scholar 

  47. Hakomori, S. & Kannagi, R. Glycosphingolipids as tumor-associated and differentiation markers. J. Natl Cancer Inst. 71, 231–251 (1983).

    CAS  PubMed  Google Scholar 

  48. Varki, A., Kannagi, R., Toole, B. & Stanley, P. in Essentials of Glycobiology [Internet] 3rd edn Ch. 47 (eds Varki, A. et al.) (Cold Spring Harbor Laboratory Press, 2017).

  49. Ihara, S. et al. Prometastatic effect of N-acetylglucosaminyltransferase V is due to modification and stabilization of active matriptase by adding beta 1–6 GlcNAc branching. J. Biol. Chem. 277, 16960–16967 (2002).

    CAS  PubMed  Google Scholar 

  50. Seidenfaden, R., Krauter, A., Schertzinger, F., Gerardy-Schahn, R. & Hildebrandt, H. Polysialic acid directs tumor cell growth by controlling heterophilic neural cell adhesion molecule interactions. Mol. Cell. Biol. 23, 5908–5918 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  51. English, N. M., Lesley, J. F. & Hyman, R. Site-specific de-N-glycosylation of CD44 can activate hyaluronan binding, and CD44 activation states show distinct threshold densities for hyaluronan binding. Cancer Res. 58, 3736–3742 (1998).

    CAS  PubMed  Google Scholar 

  52. Marsico, G., Russo, L., Quondamatteo, F. & Pandit, A. Glycosylation and integrin regulation in cancer. Trends Cancer 4, 537–552 (2018).

    CAS  PubMed  Google Scholar 

  53. Lavrsen, K. et al. Aberrantly glycosylated MUC1 is expressed on the surface of breast cancer cells and a _target for antibody-dependent cell-mediated cytotoxicity. Glycoconj. J. 30, 227–236 (2013).

    CAS  PubMed  Google Scholar 

  54. Drake, R. R., Jones, E. E., Powers, T. W. & Nyalwidhe, J. O. Altered glycosylation in prostate cancer. Adv. Cancer Res. 126, 345–382 (2015).

    CAS  PubMed  Google Scholar 

  55. Llop, E. et al. Improvement of prostate cancer diagnosis by detecting PSA glycosylation-specific changes. Theranostics 6, 1190–1204 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  56. Tanaka, T. et al. Aberrant N-glycosylation profile of serum immunoglobulins is a diagnostic biomarker of urothelial carcinomas. Int. J. Mol. Sci. 18, 2632 (2017).

    PubMed Central  Google Scholar 

  57. Peracaula, R. et al. Altered glycosylation pattern allows the distinction between prostate-specific antigen (PSA) from normal and tumor origins. Glycobiology 13, 457–470 (2003).

    CAS  PubMed  Google Scholar 

  58. Tabarés, G. et al. Different glycan structures in prostate-specific antigen from prostate cancer sera in relation to seminal plasma PSA. Glycobiology 16, 132–145 (2006).

    PubMed  Google Scholar 

  59. Jia, G. et al. Alterations in expressed prostate secretion-urine PSA N-glycosylation discriminate prostate cancer from benign prostate hyperplasia. Onco_target 8, 76987–76999 (2017).

    PubMed  PubMed Central  Google Scholar 

  60. Dal Moro, F., Valotto, C., Guttilla, A. & Zattoni, F. Urinary markers in the everyday diagnosis of bladder cancer. Urol. J. 80, 265–275 (2013).

    Google Scholar 

  61. Hautmann, S. H. et al. Hyaluronic acid and hyaluronidase. 2 new bladder carcinoma markers [German]. Urologe. A 40, 121–126 (2001).

    CAS  PubMed  Google Scholar 

  62. Cerliani, J. P., Blidner, A. G., Toscano, M. A., Croci, D. O. & Rabinovich, G. A. Translating the ‘sugar code’ into immune and vascular signaling programs. Trends Biochem. Sci. 42, 255–273 (2017).

    CAS  PubMed  Google Scholar 

  63. Hirabayashi, J. & Kasai, K. The family of metazoan metal-independent beta-galactoside-binding lectins: structure, function and molecular evolution. Glycobiology 3, 297–304 (1993).

    CAS  PubMed  Google Scholar 

  64. Di Lella, S. et al. When galectins recognize glycans: from biochemistry to physiology and back again. Biochemistry 50, 7842–7857 (2011).

    PubMed  Google Scholar 

  65. Hirabayashi, J. et al. Oligosaccharide specificity of galectins: a search by frontal affinity chromatography. Biochim. Biophys. Acta 1572, 232–254 (2002).

    CAS  PubMed  Google Scholar 

  66. Stowell, S. R. et al. Galectin-1, -2, and -3 exhibit differential recognition of sialylated glycans and blood group antigens. J. Biol. Chem. 283, 10109–10123 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  67. Greenspan, N. S. Dimensions of antigen recognition and levels of immunological specificity. Adv. Cancer Res. 80, 147–187 (2001).

    CAS  PubMed  Google Scholar 

  68. Rabinovich, G. A., Toscano, M. A., Jackson, S. S. & Vasta, G. R. Functions of cell surface galectin-glycoprotein lattices. Curr. Opin. Struct. Biol. 17, 513–520 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  69. Stowell, S. R. et al. Ligand reduces galectin-1 sensitivity to oxidative inactivation by enhancing dimer formation. J. Biol. Chem. 284, 4989–4999 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  70. Leppanen, A., Stowell, S., Blixt, O. & Cummings, R. D. Dimeric galectin-1 binds with high affinity to alpha2,3-sialylated and non-sialylated terminal N-acetyllactosamine units on surface-bound extended glycans. J. Biol. Chem. 280, 5549–5562 (2005).

    PubMed  Google Scholar 

  71. 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 20, 7486–7493 (2001).

    CAS  PubMed  Google Scholar 

  72. Elad-Sfadia, G., Haklai, R., Balan, E. & Kloog, Y. Galectin-3 augments K-Ras activation and triggers a Ras signal that attenuates ERK but not phosphoinositide 3-kinase activity. J. Biol. Chem. 279, 34922–34930 (2004).

    CAS  PubMed  Google Scholar 

  73. Salomonsson, E. et al. Monovalent interactions of galectin-1. Biochemistry 49, 9518–9532 (2010).

    CAS  PubMed  Google Scholar 

  74. Camby, I., Le Mercier, M., Lefranc, F. & Kiss, R. Galectin-1: a small protein with major functions. Glycobiology 16, 137R–157R (2006).

    CAS  PubMed  Google Scholar 

  75. Voss, P. G. et al. Dissociation of the carbohydrate-binding and splicing activities of galectin-1. Arch. Biochem. Biophys. 478, 18–25 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  76. Hughes, R. C. Secretion of the galectin family of mammalian carbohydrate-binding proteins. Biochim. Biophys. Acta 1473, 172–185 (1999).

    CAS  PubMed  Google Scholar 

  77. Leffler, H., Carlsson, S., Hedlund, M., Qian, Y. & Poirier, F. Introduction to galectins. Glycoconj. J. 19, 433–440 (2004).

    Google Scholar 

  78. Compagno, D. et al. Galectins: major signaling modulators inside and outside the cell. Curr. Mol. Med. 14, 630–651 (2014).

    CAS  PubMed  Google Scholar 

  79. Balan, V., Nangia-Makker, P. & Raz, A. Galectins as cancer biomarkers. Cancers (Basel). 2 592–610 (2010).

    Google Scholar 

  80. Jones, J. L. et al. Galectin-3 is associated with prostasomes in human semen. Glycoconj. J. 27, 227–236 (2010).

    CAS  PubMed  Google Scholar 

  81. Thijssen, V. L., Heusschen, R., Caers, J. & Griffioen, A. W. Galectin expression in cancer diagnosis and prognosis: a systematic review. Biochim. Biophys. Acta 1855, 235–247 (2015).

    CAS  PubMed  Google Scholar 

  82. Thijssen, V. L. et al. Tumor cells secrete galectin-1 to enhance endothelial cell activity. Cancer Res. 70, 6216–6224 (2010).

    CAS  PubMed  Google Scholar 

  83. Manzi, M. et al. Galectin-1 controls the proliferation and migration of liver sinusoidal endothelial cells and their interaction with hepatocarcinoma cells. J. Cell. Physiol. 231, 1522–1533 (2016).

    CAS  PubMed  Google Scholar 

  84. Yamaoka, K. et al. Expression of galectin-1 mRNA correlates with the malignant potential of human gliomas and expression of antisense galectin-1 inhibits the growth of 9 glioma cells. J. Neurosci. Res. 59, 722–730 (2000).

    CAS  PubMed  Google Scholar 

  85. Orozco, C. A. et al. _targeting galectin-1 inhibits pancreatic cancer progression by modulating tumor–stroma crosstalk. Proc. Natl Acad. Sci. USA 115, E3769–E3778 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  86. Rabinovich, G. A. et al. Specific inhibition of T cell adhesion to extracellular matrix and proinflammatory cytokine secretion by human recombinant galectin-1. Immunology 97, 100–106 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  87. Rabinovich, G. A., Toscano, M. A., Ilarregui, J. M. & Rubinstein, N. Shedding light on the immunomodulatory properties of galectins: novel regulators of innate and adaptive immune responses. Glycoconj. J. 19, 565–573 (2004).

    Google Scholar 

  88. Liu, F. T. & Rabinovich, G. A. Galectins as modulators of tumour progression. Nat. Rev. Cancer 5, 29–41 (2005).

    CAS  PubMed  Google Scholar 

  89. Gao, X., Liu, J., Liu, X., Li, L. & Zheng, J. Cleavage and phosphorylation: important post-translational modifications of galectin-3. Cancer Metastasis Rev. 36, 367–374 (2017).

    CAS  PubMed  Google Scholar 

  90. Mazurek, N., Conklin, J., Byrd, J. C., Raz, A. & Bresalier, R. S. Phosphorylation of the beta-galactoside-binding protein galectin-3 modulates binding to its ligands. J. Biol. Chem. 275, 36311–36315 (2000).

    CAS  PubMed  Google Scholar 

  91. Yoshii, T. et al. Galectin-3 phosphorylation is required for its anti-apoptotic function and cell cycle arrest. J. Biol. Chem. 277, 6852–6857 (2002).

    PubMed  Google Scholar 

  92. Danguy, A., Camby, I. & Kiss, R. Galectins and cancer. Biochim. Biophys. Acta 1572, 285–293 (2002).

    CAS  PubMed  Google Scholar 

  93. van den, B. F., Califice, S. & Castronovo, V. Expression of galectins in cancer: a critical review. Glycoconj. J. 19, 537–542 (2004).

    Google Scholar 

  94. Yang, R. Y., Rabinovich, G. A. & Liu, F. T. Galectins: structure, function and therapeutic potential. Expert. Rev. Mol. Med. 10, e17 (2008).

    PubMed  Google Scholar 

  95. Teichberg, V. I., Silman, I., Beitsch, D. D. & Resheff, G. A beta-D-galactoside binding protein from electric organ tissue of Electrophorus electricus. Proc. Natl Acad. Sci. USA 72, 1383–1387 (1975).

    CAS  PubMed  PubMed Central  Google Scholar 

  96. Raz, A. & Lotan, R. Endogenous galactoside-binding lectins: a new class of functional tumor cell surface molecules related to metastasis. Cancer Metastasis Rev. 6, 433–452 (1987).

    CAS  PubMed  Google Scholar 

  97. Raz, A. & Lotan, R. Lectin-like activities associated with human and murine neoplastic cells. Cancer Res. 41, 3642–3647 (1981).

    CAS  PubMed  Google Scholar 

  98. Elad-Sfadia, G., Haklai, R., Ballan, E., Gabius, H. J. & Kloog, Y. Galectin-1 augments Ras activation and diverts Ras signals to Raf-1 at the expense of phosphoinositide 3-kinase. J. Biol. Chem. 277, 37169–37175 (2002).

    CAS  PubMed  Google Scholar 

  99. Andre, S. et al. Galectins-1 and -3 and their ligands in tumor biology. J. Cancer Res. Clin. Oncol. 125, 461–474 (1999).

    CAS  PubMed  Google Scholar 

  100. Gu, M., Wang, W., Song, W. K., Cooper, D. N. & Kaufman, S. J. Selective modulation of the interaction of alpha 7 beta 1 integrin with fibronectin and laminin by L-14 lectin during skeletal muscle differentiation. J. Cell Sci. 107, 175–181 (1994).

    CAS  PubMed  Google Scholar 

  101. Shimura, T. et al. Implication of galectin-3 in Wnt signaling. Cancer Res. 65, 3535–3537 (2005).

    CAS  PubMed  Google Scholar 

  102. Shimura, T. et al. Galectin-3, a novel binding partner of β-catenin. Cancer Res. 64, 6363–6367 (2004).

    CAS  PubMed  Google Scholar 

  103. Martinez-Bosch, N. et al. Galectin-1 drives pancreatic carcinogenesis through stroma remodeling and hedgehog signaling activation. Cancer Res. 74, 3512–3524 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  104. Rabinovich, G. A. et al. Induction of allogenic T cell hyporesponsiveness by galectin-1-mediated apoptotic and non-apoptotic mechanisms. Cell Death. Differ. 9, 661–670 (2002).

    CAS  PubMed  Google Scholar 

  105. He, J. & Baum, L. G. Presentation of galectin-1 by extracellular matrix triggers T cell death. J. Biol. Chem. 279, 4705–4712 (2004).

    CAS  PubMed  Google Scholar 

  106. Ebrahim, A. H. et al. Galectins in cancer: carcinogenesis, diagnosis and therapy. Ann. Transl Med. 2, 88 (2014).

    PubMed  PubMed Central  Google Scholar 

  107. Rabinovich, G. A. & Conejo-García, J. R. Shaping the immune landscape in cancer by galectin-driven regulatory pathways. J. Mol. Biol. 428, 3266–3281 (2016).

    CAS  PubMed  Google Scholar 

  108. Colnot, C., Fowlis, D., Ripoche, M. A., Bouchaert, I. & Poirier, F. Embryonic implantation in galectin 1/galectin 3 double mutant mice. Dev. Dyn. 211, 306–313 (1998).

    CAS  PubMed  Google Scholar 

  109. Wang, W., Park, J. W., Wang, J. L. & Patterson, R. J. Immunoprecipitation of spliceosomal RNAs by antisera to galectin-1 and galectin-3. Nucleic Acids Res. 34, 5166–5174 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  110. Demydenko, D. & Berest, I. Expression of galectin-1 in malignant tumors. Exp. Oncol. 31, 74–79 (2009).

    CAS  PubMed  Google Scholar 

  111. Blanchard, H., Bum-Erdene, K., Bohari, M. H. & Yu, X. Galectin-1 inhibitors and their potential therapeutic applications: a patent review. Expert Opin. Ther. Pat. 26, 537–554 (2016).

    CAS  PubMed  Google Scholar 

  112. Laderach, D. J. et al. A unique galectin signature in human prostate cancer progression suggests galectin-1 as a key _target for treatment of advanced disease. Cancer Res. 73, 86–96 (2013).

    CAS  PubMed  Google Scholar 

  113. Compagno, D. et al. Glycans and galectins in prostate cancer biology, angiogenesis and metastasis. Glycobiology 24, 899–906 (2014).

    CAS  PubMed  Google Scholar 

  114. Ellerhorst, J., Troncoso, P., Xu, X. C., Lee, J. & Lotan, R. Galectin-1 and galectin-3 expression in human prostate tissue and prostate cancer. Urol. Res. 27, 362–367 (1999).

    CAS  PubMed  Google Scholar 

  115. Ellerhorst, J., Nguyen, T., Cooper, D. N., Lotan, D. & Lotan, R. Differential expression of endogenous galectin-1 and galectin-3 in human prostate cancer cell lines and effects of overexpressing galectin-1 on cell phenotype. Int. J. Oncol. 14, 217–224 (1999).

    CAS  PubMed  Google Scholar 

  116. Clausse, N., van den Brûle, F., Waltregny, D., Garnier, F. & Castronovo, V. Galectin-1 expression in prostate tumor-associated capillary endothelial cells is increased by prostate carcinoma cells and modulates heterotypic cell-cell adhesion. Angiogenesis 3, 317–325 (1999).

    CAS  PubMed  Google Scholar 

  117. van den Brûle, F. A., Waltregny, D. & Castronovo, V. Increased expression of galectin-1 in carcinoma-associated stroma predicts poor outcome in prostate carcinoma patients. J. Pathol. 193, 80–87 (2001).

    PubMed  Google Scholar 

  118. He, J. & Baum, L. G. Endothelial cell expression of galectin-1 induced by prostate cancer cells inhibits T cell transendothelial migration. Lab. Invest. 86, 578–590 (2006).

    CAS  PubMed  Google Scholar 

  119. Valenzuela, H. F. et al. O-glycosylation regulates LNCaP prostate cancer cell susceptibility to apoptosis induced by galectin-1. Cancer Res. 67, 6155–6162 (2007).

    CAS  PubMed  Google Scholar 

  120. Petrosyan, A., Holzapfel, M. S., Muirhead, D. E. & Cheng, P.-W. Restoration of compact Golgi morphology in advanced prostate cancer enhances susceptibility to galectin-1-induced apoptosis by modifying mucin O-glycan synthesis. Mol. Cancer Res. 12, 1704–1716 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  121. Shih, T.-C. et al. _targeting galectin-1 impairs castration-resistant prostate cancer progression and invasion. Clin. Cancer Res. 24, 4319–4331 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  122. Andersen, H., Jensen, O. N., Moiseeva, E. P. & Eriksen, E. F. A proteome study of secreted prostatic factors affecting osteoblastic activity: galectin-1 is involved in differentiation of human bone marrow stromal cells. J. Bone Miner. Res. 18, 195–203 (2003).

    CAS  PubMed  Google Scholar 

  123. Jaworski, F. M. et al. In VivoHemin conditioning _targets the vascular and immunologic compartments and restrains prostate tumor development. Clin. Cancer Res. 23, 5135–5148 (2017).

    CAS  PubMed  Google Scholar 

  124. Corapi, E., Carrizo, G., Compagno, D. & Laderach, D. Endogenous galectin-1 in T lymphocytes regulates anti-prostate cancer immunity. Front. Immunol. 9, 2190 (2018).

    PubMed  PubMed Central  Google Scholar 

  125. Pacis, R. A. et al. Decreased galectin-3 expression in prostate cancer. Prostate 44, 118–123 (2000).

    CAS  PubMed  Google Scholar 

  126. Merseburger, A. S. et al. Involvement of decreased galectin-3 expression in the pathogenesis and progression of prostate cancer. Prostate 68, 72–77 (2008).

    PubMed  Google Scholar 

  127. Wang, Y. et al. Regulation of prostate cancer progression by galectin-3. Am. J. Pathol. 174, 1515–1523 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  128. de Melo-Júnior, M. R., Araújo-Filho, J. L. S., Lins, C. A. B., de Pontes-Filho, N. T. & de Carvalho, L. B. Immobilization of anti-galectin-3 onto polysiloxane-polyvinyl alcohol disks for tumor prostatic diseases diagnosis. Appl. Biochem. Biotechnol. 160, 2198–2207 (2010).

    PubMed  Google Scholar 

  129. Knapp, J. S. et al. Galectin-3 expression in prostate cancer and benign prostate tissues: correlation with biochemical recurrence. World J. Urol. 31, 351–358 (2013).

    CAS  PubMed  Google Scholar 

  130. Geisler, C. et al. Identification and validation of potential new biomarkers for prostate cancer diagnosis and prognosis using 2D-DIGE and MS. Biomed. Res. Int. 2015, 454256 (2015).

    PubMed  PubMed Central  Google Scholar 

  131. van den Brûle, F. A., Waltregny, D., Liu, F. T. & Castronovo, V. Alteration of the cytoplasmic/nuclear expression pattern of galectin-3 correlates with prostate carcinoma progression. Int. J. Cancer 89, 361–367 (2000).

    PubMed  Google Scholar 

  132. Ahmed, H., Banerjee, P. P. & Vasta, G. R. Differential expression of galectins in normal, benign and malignant prostate epithelial cells: silencing of galectin-3 expression in prostate cancer by its promoter methylation. Biochem. Biophys. Res. Commun. 358, 241–246 (2007).

    CAS  PubMed  Google Scholar 

  133. 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 versus tumor promotion of cytoplasmic galectin-3. Oncogene 23, 7527–7536 (2004).

    CAS  PubMed  Google Scholar 

  134. Fukumori, T. et al. Galectin-3 regulates mitochondrial stability and antiapoptotic function in response to anticancer drug in prostate cancer. Cancer Res. 66, 3114–3119 (2006).

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  PubMed Central  Google Scholar 

  136. Dondoo, T.-O. et al. Galectin-3 is implicated in tumor progression and resistance to anti-androgen drug through regulation of androgen receptor signaling in prostate cancer. Anticancer Res. 37, 125–134 (2017).

    CAS  PubMed  Google Scholar 

  137. Guha, P. et al. Cod glycopeptide with picomolar affinity to galectin-3 suppresses T cell apoptosis and prostate cancer metastasis. Proc. Natl Acad. Sci. USA 110, 5052–5057 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  138. Glinsky, V. V. et al. The role of Thomsen-Friedenreich antigen in adhesion of human breast and prostate cancer cells to the endothelium. Cancer Res. 61, 4851–4857 (2001).

    CAS  PubMed  Google Scholar 

  139. Glinsky, V. V. et al. Intravascular metastatic cancer cell homotypic aggregation at the sites of primary attachment to the endothelium. Cancer Res. 63, 3805–3811 (2003).

    CAS  PubMed  Google Scholar 

  140. Meng, F., Joshi, B. & Nabi, I. R. Galectin-3 overrides PTRF/Cavin-1 reduction of PC3 prostate cancer cell migration. PLOS ONE 10, e0126056 (2015).

    PubMed  PubMed Central  Google Scholar 

  141. Farhad, M., Rolig, A. S. & Redmond, W. L. The role of Galectin-3 in modulating tumor growth and immunosuppression within the tumor microenvironment. Oncoimmunology 7, e1434467 (2018).

    PubMed  PubMed Central  Google Scholar 

  142. Lee, Y.-C. et al. Secretome analysis of an osteogenic prostate tumor identifies complex signaling networks mediating cross-talk of cancer and stromal cells within the tumor microenvironment. Mol. Cell. Proteomics 14, 471–483 (2015).

    CAS  PubMed  Google Scholar 

  143. Nakajima, K. et al. Galectin-3 cleavage alters bone remodeling: different outcomes in breast and prostate cancer skeletal metastasis. Cancer Res. 76, 1391–1402 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  144. Pienta, K. J. et al. Inhibition of spontaneous metastasis in a rat prostate cancer model by oral administration of modified citrus pectin. J. Natl Cancer Inst. 87, 348–353 (1995).

    CAS  PubMed  Google Scholar 

  145. Glinskii, O. V. et al. Inhibition of prostate cancer bone metastasis by synthetic TF antigen mimic/galectin-3 inhibitor lactulose-L-leucine. Neoplasia 14, 65–73 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  146. Nakajima, K. et al. Positive associations between galectin-3 and PSA levels in prostate cancer patients: a prospective clinical study-I. Onco_target 7, 82266–82272 (2016).

    PubMed  PubMed Central  Google Scholar 

  147. Nakajima, K. et al. The influence of PSA autoantibodies in prostate cancer patients: a prospective clinical study-II. Onco_target 8, 17643–17650 (2017).

    PubMed  Google Scholar 

  148. Ochieng, J. et al. Galectin-3 is a novel substrate for human matrix metalloproteinases-2 and -9. Biochemistry 33, 14109–14114 (1994).

    CAS  PubMed  Google Scholar 

  149. Saraswati, S. et al. Galectin-3 is a substrate for prostate specific antigen (PSA) in human seminal plasma. Prostate 71, 197–208 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  150. Yang, Y. et al. Treatment of prostate carcinoma with (galectin-3)-_targeted HPMA copolymer-(G3-C12)-5-Fluorouracil conjugates. Biomaterials 33, 2260–2271 (2012).

    CAS  PubMed  Google Scholar 

  151. Glinsky, V. V. & Raz, A. Modified citrus pectin anti-metastatic properties: one bullet, multiple _targets. Carbohydr. Res. 344, 1788–1791 (2009).

    CAS  PubMed  Google Scholar 

  152. Conti, S. et al. Modified citrus pectin as a potential sensitizer for radiotherapy in prostate cancer. Integr. Cancer Ther. 17, 1225–1234 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  153. Tsai, C.-H. et al. Metastatic progression of prostate cancer is mediated by autonomous binding of galectin-4- O -glycan to cancer cells. Cancer Res. 76, 5756–5767 (2016).

    CAS  PubMed  Google Scholar 

  154. Tzeng, S.-F. et al. O-Glycosylation-mediated signaling circuit drives metastatic castration-resistant prostate cancer. FASEB J. 32, fj201800687 (2018).

    Google Scholar 

  155. Labrie, M. et al. A mutation in the carbohydrate recognition domain drives a phenotypic switch in the role of galectin-7 in prostate cancer. PLOS ONE 10, e0131307 (2015).

    PubMed  PubMed Central  Google Scholar 

  156. Su, Z. Z. et al. Surface-epitope masking and expression cloning identifies the human prostate carcinoma tumor antigen gene PCTA-1 a member of the galectin gene family. Proc. Natl Acad. Sci. USA 93, 7252–7257 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  157. Gopalkrishnan, R. V. et al. Molecular characterization of prostate carcinoma tumor antigen-1, PCTA-1, a human galectin-8 related gene. Oncogene 19, 4405–4416 (2000).

    CAS  PubMed  Google Scholar 

  158. Danguy, A. et al. Immunohistochemical profile of galectin-8 expression in benign and malignant tumors of epithelial, mesenchymatous and adipous origins, and of the nervous system. Histol. Histopathol. 16, 861–868 (2001).

    CAS  PubMed  Google Scholar 

  159. Nguyen, M. C. et al. Antibody responses to galectin-8, TARP and TRAP1 in prostate cancer patients treated with a GM-CSF-secreting cellular immunotherapy. Cancer Immunol. Immunother. 59, 1313–1323 (2010).

    CAS  PubMed  Google Scholar 

  160. Gentilini, L. D. et al. Stable and high expression of galectin-8 tightly controls metastatic progression of prostate cancer. Onco_target 8, 44654–44668 (2017).

    PubMed  PubMed Central  Google Scholar 

  161. GuhaThakurta, D. et al. Humoral immune response against non_targeted tumor antigens after treatment with Sipuleucel-T and its association with improved clinical outcome. Clin. Cancer Res. 21, 3619–3630 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  162. Cindolo, L. et al. Galectin-1 and galectin-3 expression in human bladder transitional-cell carcinomas. Int. J. Cancer 84, 39–43 (1999).

    CAS  PubMed  Google Scholar 

  163. Chuang, C.-H. et al. Lab on a chip for multiplexed immunoassays to detect bladder cancer using multifunctional dielectrophoretic manipulations. Lab. Chip 15, 3056–3064 (2015).

    CAS  PubMed  Google Scholar 

  164. Shen, K.-H. et al. Role of galectin-1 in urinary bladder urothelial carcinoma cell invasion through the JNK pathway. Cancer Sci. 107, 1390–1398 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  165. Li, C.-F. et al. Proteomic identification of the galectin-1-involved molecular pathways in urinary bladder urothelial carcinoma. Int. J. Mol. Sci. 19, 1242 (2018).

    PubMed Central  Google Scholar 

  166. Fang, T. et al. Modified citrus pectin inhibited bladder tumor growth through downregulation of galectin-3. Acta Pharmacol. Sin. 39, 1885–1893 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  167. Matsui, Y. et al. Sensitizing effect of galectin-7 in urothelial cancer to cisplatin through the accumulation of intracellular reactive oxygen species. Cancer Res. 67, 1212–1220 (2007).

    CAS  PubMed  Google Scholar 

  168. Kramer, M. W. et al. Decreased galectin-8 is a strong marker for recurrence in urothelial carcinoma of the bladder. Urol. Int. 87, 143–150 (2011).

    CAS  PubMed  Google Scholar 

  169. Griffioen, A. W. & Thijssen, V. L. Galectins in tumor angiogenesis. Ann. Transl Med. 2, 90 (2014).

    PubMed  PubMed Central  Google Scholar 

  170. Méndez-Huergo, S. P., Blidner, A. G. & Rabinovich, G. A. Galectins: emerging regulatory checkpoints linking tumor immunity and angiogenesis. Curr. Opin. Immunol. 45, 8–15 (2017).

    PubMed  Google Scholar 

  171. Tsuboi, S. et al. A novel strategy for evasion of NK cell immunity by tumours expressing core2 O-glycans. EMBO J. 30, 3173–3185 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  172. Wang, W. et al. Tumor-released galectin-3, a soluble inhibitory ligand of human NKp30, plays an important role in tumor escape from NK cell attack. J. Biol. Chem. 289, 33311–33319 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  173. Li, H. et al. Tim-3/galectin-9 signaling pathway mediates T cell dysfunction and predicts poor prognosis in patients with hepatitis B virus-associated hepatocellular carcinoma. Hepatology 56, 1342–1351 (2012).

    CAS  PubMed  Google Scholar 

  174. Kang, C.-W. et al. Apoptosis of tumor infiltrating effector TIM-3+CD8+ T cells in colon cancer. Sci. Rep. 5, 15659 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  175. Dardalhon, V. et al. Tim-3/galectin-9 pathway: regulation of Th1 immunity through promotion of CD11b+Ly-6G+ myeloid cells. J. Immunol. 185, 1383–1392 (2010).

    CAS  PubMed  Google Scholar 

  176. US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT01724320 (2012).

  177. Delord, J.-P. et al. A first-in-man phase I study of the galectin-1 (gal-1) inhibitor OTX008 given subcutaneously as a single agent to patients with advanced solid tumors [abstract]. Mol. Cancer Ther. 12 (Suppl. 11), A72 (2013).

    Google Scholar 

  178. US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT054977 (2012).

  179. US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT00110721 (2012).

  180. Klyosov, A., Zomer, E. & Platt, D. in Glycobiology and Drug Design (ed. Klyosov, A. A.) 89–130 (American Chemical Society, 2012).

  181. US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT01723813 (2019).

  182. Linch, S. et al. Galectin-3 inhibition using novel inhibitor GR-MD-02 improves survival and immune function while reducing tumor vasculature. J. Immunother. Cancer 3, 306 (2015).

    Google Scholar 

  183. US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT02117362 (2019).

  184. US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT02575404 (2018).

  185. Pérez, C. V. et al. Dual roles of endogenous and exogenous galectin-1 in the control of testicular immunopathology. Sci. Rep. 5, 12259 (2015).

    PubMed  PubMed Central  Google Scholar 

  186. Paclik, D. et al. Galectin-2 induces apoptosis of lamina propria T lymphocytes and ameliorates acute and chronic experimental colitis in mice. J. Mol. Med. 86, 1395–1406 (2008).

    CAS  PubMed  Google Scholar 

  187. López, E. et al. Inhibition of chronic airway inflammation and remodeling by galectin-3 gene therapy in a murine model. J. Immunol. 176, 1943–1950 (2006).

    PubMed  Google Scholar 

  188. Watanabe, M. et al. Clinical significance of circulating galectins as colorectal cancer markers. Oncol. Rep. 25, 1217–1226 (2011).

    PubMed  Google Scholar 

  189. Verschuere, T. et al. Altered galectin-1 serum levels in patients diagnosed with high-grade glioma. J. Neurooncol. 115, 9–17 (2013).

    CAS  PubMed  Google Scholar 

  190. Ouyang, J. et al. Galectin-1 serum levels reflect tumor burden and adverse clinical features in classical Hodgkin lymphoma. Blood 121, 3431–3433 (2013).

    CAS  PubMed  Google Scholar 

  191. Aggarwal, S., Sharma, S. C. & Das, S. N. Galectin-1 and galectin-3: plausible tumour markers for oral squamous cell carcinoma and suitable _targets for screening high-risk population. Clin. Chim. Acta 442, 13–21 (2015).

    CAS  PubMed  Google Scholar 

  192. Kaneko, N. et al. Potential tumor markers of renal cell carcinoma: α-Enolase for postoperative follow up, and galectin-1 and galectin-3 for primary detection. Int. J. Urol. 20, 530–535 (2013).

    CAS  PubMed  Google Scholar 

  193. Waalkes, S., Merseburger, A. S., Simon, A., Serth, J. & Kuczyk, M. A. Galectin-expression an urologischen tumoren [German]. Urologe 49, 387–391 (2010).

    CAS  Google Scholar 

  194. El Gendy, H. et al. Galectin 3 for the diagnosis of bladder cancer. Arab J. Urol. 12, 178–181 (2014).

    PubMed  Google Scholar 

  195. Poirier, F. & Robertson, E. J. Normal development of mice carrying a null mutation in the gene encoding the L14 S-type lectin. Development 119, 1229–1236 (1993).

    CAS  PubMed  Google Scholar 

  196. Sundblad, V., Morosi, L. G., Geffner, J. R. & Rabinovich, G. A. Galectin-1: a jack-of-all-trades in the resolution of acute and chronic inflammation. J. Immunol. 199, 3721–3730 (2017).

    CAS  PubMed  Google Scholar 

  197. Arthur, C. M., Baruffi, M. D., Cummings, R. D. & Stowell, S. R. Evolving mechanistic insights into galectin functions. Methods Mol. Biol. 1207, 1–35 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  198. Croci, D. O. et al. Disrupting galectin-1 interactions with N-glycans suppresses hypoxia-driven angiogenesis and tumorigenesis in Kaposi’s sarcoma. J. Exp. Med. 209, 1985–2000 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  199. Ouyang, J. et al. Viral induction and _targeted inhibition of galectin-1 in EBV+ posttransplant lymphoproliferative disorders. Blood 117, 4315–4322 (2011).

    CAS  PubMed  Google Scholar 

  200. Becher, O. J. & Holland, E. C. Genetically engineered models have advantages over xenografts for preclinical studies. Cancer Res. 66, 3355–3358 (2006).

    CAS  PubMed  Google Scholar 

  201. Day, C.-P., Merlino, G. & Van Dyke, T. Preclinical mouse cancer models: a maze of opportunities and challenges. Cell 163, 39–53 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  202. Grabowska, M. M. et al. Mouse models of prostate cancer: picking the best model for the question. Cancer Metastasis Rev. 33, 377–397 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  203. Rea, D. et al. Mouse models in prostate cancer translational research: from xenograft to PDX. Biomed. Res. Int. 2016, 9750795 (2016).

    PubMed  PubMed Central  Google Scholar 

  204. Kobayashi, T., Owczarek, T. B., McKiernan, J. M. & Abate-Shen, C. Modelling bladder cancer in mice: opportunities and challenges. Nat. Rev. Cancer 15, 42–54 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  205. Eisenstein, M. Organoids: the body builders. Nat. Methods 15, 19–22 (2018).

    CAS  Google Scholar 

  206. Vela, I. & Chen, Y. Prostate cancer organoids: a potential new tool for testing drug sensitivity. Expert Rev. Anticancer Ther. 15, 261–263 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  207. Gao, D. et al. Organoid cultures derived from patients with advanced prostate cancer. Cell 159, 176–187 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  208. Karthaus, W. R. et al. Identification of multipotent luminal progenitor cells in human prostate organoid cultures. Cell 159, 163–175 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  209. Lee, S. H. et al. Tumor evolution and drug response in patient-derived organoid models of bladder cancer. Cell 173, 515–528 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  210. Yoshida, T., Singh, A. K., Bishai, W. R., McConkey, D. J. & Bivalacqua, T. J. Organoid culture of bladder cancer cells. Investig. Clin. Urol. 59, 149 (2018).

    PubMed  PubMed Central  Google Scholar 

  211. Wang, S., Gao, D. & Chen, Y. The potential of organoids in urological cancer research. Nat. Rev. Urol. 14, 401–414 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  212. Kantoff, P. W. et al. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N. Engl. J. Med. 363, 411–422 (2010).

    CAS  PubMed  Google Scholar 

  213. Goswami, S., Aparicio, A. & Subudhi, S. K. Immune checkpoint therapies in prostate cancer. Cancer J. 22, 117–120 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  214. Beer, T. M. et al. Randomized, double-blind, phase III trial of ipilimumab versus placebo in asymptomatic or minimally symptomatic patients with metastatic chemotherapy-naive castration-resistant prostate cancer. J. Clin. Oncol. 35, 40–47 (2017).

    CAS  PubMed  Google Scholar 

  215. Fakhrejahani, F. et al. Avelumab in metastatic castration-resistant prostate cancer (mCRPC). J. Clin. Oncol. 35, 159–159 (2017).

    Google Scholar 

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Acknowledgements

This work was supported by grants from the Spanish Ministry of Economy and Competitiveness/ISCIII-FEDER (PI14/00125 and PI17/00199), an AECC-Cataluña 2015 grant and the Generalitat de Catalunya (2014/SGR/143 and 2017/SGR/225) grant to P.N. The authors thank V. A. Raker for valuable comments and input on language.

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Nature Reviews Urology thanks V. V. Glinsky, P. Nangia-Makker and other anonymous reviewer(s) for their contribution to the peer review of this work.

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Authors and Affiliations

  1. Cancer Research Program, Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain

    Neus Martínez-Bosch, Alejo Rodriguez-Vida, Ana Rovira, Joan Albanell, Joaquim Bellmunt & Pilar Navarro

  2. Unidad Asociada I+D+i Hospital del Mar Medical Research Institute (IMIM)-Institute of Biomedical Research of Barcelona (IIBB-CSIC), Barcelona, Spain

    Neus Martínez-Bosch & Pilar Navarro

  3. Department of Medical Oncology, Hospital del Mar, Barcelona, Spain

    Alejo Rodriguez-Vida & Joan Albanell

  4. Department of Pathology, Hospital del Mar, Barcelona, Spain

    Núria Juanpere & Josep Lloreta

  5. Bladder Cancer Center, Dana-Farber Cancer Institute/Brigham and Women’s Cancer Center, Harvard Medical School, Boston, MA, USA

    Joaquim Bellmunt

  6. Institute of Biomedical Research of Barcelona (IIBB-CSIC), Barcelona, Spain

    Pilar Navarro

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Martínez-Bosch, N., Rodriguez-Vida, A., Juanpere, N. et al. Galectins in prostate and bladder cancer: tumorigenic roles and clinical opportunities. Nat Rev Urol 16, 433–445 (2019). https://doi.org/10.1038/s41585-019-0183-5

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