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Galectin-1 as a potent target for cancer therapy: role in the tumor microenvironment

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Abstract

The microenvironment of a tumor is a highly complex milieu, primarily characterized by immunosuppression, abnormal angiogenesis, and hypoxic regions. These features promote tumor progression and metastasis, resulting in poor prognosis and greater resistance to existing cancer therapies. Galectin-1 is a β-galactoside binding protein that is abundantly secreted by almost all types of malignant tumor cells. The expression of galectin-1 is regulated by hypoxia-inducible factor-1 (HIF-1) and it plays vital pro-tumorigenic roles within the tumor microenvironment. In particular, galectin-1 suppresses T cell-mediated cytotoxic immune responses and promotes tumor angiogenesis. However, since galectin-1 displays many different activities by binding to a number of diverse N- or O-glycan modified target proteins, it has been difficult to fully understand how galectin-1 supports tumor growth and metastasis. This review explores the importance of galectin-1 and glycan expression patterns in the tumor microenvironment and the potential effects of inhibiting galectin-1 as a therapeutic target for cancer treatment.

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References

  1. Barondes, S. H., Castronovo, V., Cooper, D. N., Cummings, R. D., Drickamer, K., Feizi, T., et al. (1994). Galectins: a family of animal beta-galactoside-binding lectins. Cell, 76(4), 597–598.

    PubMed  CAS  Google Scholar 

  2. Cooper, D. N. (2002). Galectinomics: finding themes in complexity. Biochimica et Biophysica Acta, 1572(2–3), 209–231.

    PubMed  CAS  Google Scholar 

  3. Yang, R. Y., Rabinovich, G. A., & Liu, F. T. (2008). Galectins: structure, function and therapeutic potential. Expert Reviews in Molecular Medicine, 10, e17.

    PubMed  Google Scholar 

  4. Than, N. G., Romero, R., Erez, O., Weckle, A., Tarca, A. L., Hotra, J., et al. (2008). Emergence of hormonal and redox regulation of galectin-1 in placental mammals: implication in maternal-fetal immune tolerance. Proceedings of the National Academy of Sciences of the United States of America, 105(41), 15819–15824.

    PubMed  CAS  Google Scholar 

  5. Bourne, Y., Bolgiano, B., Nesa, M. P., Penfold, P., Johnson, D., Feizi, T., et al. (1994). Crystallization and preliminary X-ray diffraction studies of the soluble 14 kDa beta-galactoside-binding lectin from bovine heart. Journal of Molecular Biology, 235(2), 787–789.

    PubMed  CAS  Google Scholar 

  6. Kadoya, T., & Horie, H. (2005). Structural and functional studies of galectin-1: a novel axonal regeneration-promoting activity for oxidized galectin-1. Current Drug Targets, 6(4), 375–383.

    PubMed  CAS  Google Scholar 

  7. Scott, S. A., Bugarcic, A., & Blanchard, H. (2009). Characterisation of oxidized recombinant human galectin-1. Protein and Peptide Letters, 16(10), 1249–1255.

    PubMed  CAS  Google Scholar 

  8. Inagaki, Y., Sohma, Y., Horie, H., Nozawa, R., & Kadoya, T. (2000). Oxidized galectin-1 promotes axonal regeneration in peripheral nerves but does not possess lectin properties. European Journal of Biochemistry, 267(10), 2955–2964.

    PubMed  CAS  Google Scholar 

  9. Horie, H., Kadoya, T., Hikawa, N., Sango, K., Inoue, H., Takeshita, K., et al. (2004). Oxidized galectin-1 stimulates macrophages to promote axonal regeneration in peripheral nerves after axotomy. The Journal of Neuroscience, 24(8), 1873–1880.

    PubMed  CAS  Google Scholar 

  10. Demydenko, D., & Berest, I. (2009). Expression of galectin-1 in malignant tumors. Experimental Oncology, 31(2), 74–79.

    PubMed  CAS  Google Scholar 

  11. Thijssen, V. L., Poirier, F., Baum, L. G., & Griffioen, A. W. (2007). Galectins in the tumor endothelium: opportunities for combined cancer therapy. Blood, 110(8), 2819–2827.

    PubMed  CAS  Google Scholar 

  12. Garin, M. I., Chu, C. C., Golshayan, D., Cernuda-Morollon, E., Wait, R., & Lechler, R. I. (2007). Galectin-1: a key effector of regulation mediated by CD4+ CD25+ T cells. Blood, 109(5), 2058–2065.

    PubMed  CAS  Google Scholar 

  13. Camby, I., Le Mercier, M., Lefranc, F., & Kiss, R. (2006). Galectin-1: a small protein with major functions. Glycobiology, 16(11), 137R–157R.

    PubMed  CAS  Google Scholar 

  14. Honjo, Y., Inohara, H., Akahani, S., Yoshii, T., Takenaka, Y., Yoshida, J., et al. (2000). Expression of cytoplasmic galectin-3 as a prognostic marker in tongue carcinoma. Clinical Cancer Research, 6(12), 4635–4640.

    PubMed  CAS  Google Scholar 

  15. Cho, M., & Cummings, R. D. (1995). Galectin-1, a beta-galactoside-binding lectin in Chinese hamster ovary cells. II. Localization and biosynthesis. Journal of Biological Chemistry, 270(10), 5207–5212.

    PubMed  CAS  Google Scholar 

  16. Cho, M., & Cummings, R. D. (1995). Galectin-1, a beta-galactoside-binding lectin in Chinese hamster ovary cells. I. Physical and chemical characterization. The Journal of Biological Chemistry, 270(10), 5198–5206.

    PubMed  CAS  Google Scholar 

  17. Inohara, H., Akahani, S., & Raz, A. (1998). Galectin-3 stimulates cell proliferation. Experimental Cell Research, 245(2), 294–302.

    PubMed  CAS  Google Scholar 

  18. Baptiste, T. A., James, A., Saria, M., & Ochieng, J. (2007). Mechano-transduction mediated secretion and uptake of galectin-3 in breast carcinoma cells: implications in the extracellular functions of the lectin. Experimental Cell Research, 313(4), 652–664.

    PubMed  CAS  Google Scholar 

  19. Satelli, A., Rao, P. S., Gupta, P. K., Lockman, P. R., Srivenugopal, K. S., & Rao, U. S. (2008). Varied expression and localization of multiple galectins in different cancer cell lines. Oncology Reports, 19(3), 587–594.

    PubMed  CAS  Google Scholar 

  20. Nickel, W. (2005). Unconventional secretory routes: direct protein export across the plasma membrane of mammalian cells. Traffic, 6(8), 607–614.

    PubMed  CAS  Google Scholar 

  21. Watanabe, M., Takemasa, I., Kaneko, N., Yokoyama, Y., Matsuo, E., Iwasa, S., et al. (2011). Clinical significance of circulating galectins as colorectal cancer markers. Oncology Reports, 25(5), 1217–1226.

    PubMed  Google Scholar 

  22. Carlsson, M. C., Cederfur, C., Schaar, V., Balog, C. I., Lepur, A., Touret, F., et al. (2011). Galectin-1-binding glycoforms of haptoglobin with altered intracellular trafficking, and increase in metastatic breast cancer patients. PLoS One, 6(10), e26560.

    PubMed  CAS  Google Scholar 

  23. Saussez, S., Lorfevre, F., Lequeux, T., Laurent, G., Chantrain, G., Vertongen, F., et al. (2008). The determination of the levels of circulating galectin-1 and -3 in HNSCC patients could be used to monitor tumor progression and/or responses to therapy. Oral Oncology, 44(1), 86–93.

    PubMed  CAS  Google Scholar 

  24. Saussez, S., Glinoer, D., Chantrain, G., Pattou, F., Carnaille, B., Andre, S., et al. (2008). Serum galectin-1 and galectin-3 levels in benign and malignant nodular thyroid disease. Thyroid, 18(7), 705–712.

    PubMed  CAS  Google Scholar 

  25. Barrow, H., Guo, X., Wandall, H. H., Pedersen, J. W., Fu, B., Zhao, Q., et al. (2011). Serum galectins -2, -4 and -8 are greatly increased in colon and breast cancer patients and promote cancer cell adhesion to blood vascular endothelium. Clinical Cancer Research, 15;17(22):7035–7046

    Google Scholar 

  26. Pacienza, N., Pozner, R. G., Bianco, G. A., D'Atri, L. P., Croci, D. O., Negrotto, S., et al. (2008). The immunoregulatory glycan-binding protein galectin-1 triggers human platelet activation. The FASEB Journal, 22(4), 1113–1123.

    CAS  Google Scholar 

  27. Chiang, W. F., Liu, S. Y., Fang, L. Y., Lin, C. N., Wu, M. H., Chen, Y. C., et al. (2008). Overexpression of galectin-1 at the tumor invasion front is associated with poor prognosis in early-stage oral squamous cell carcinoma. Oral Oncology, 44(4), 325–334.

    PubMed  CAS  Google Scholar 

  28. Kim, H. J., Jeon, H. K., Cho, Y. J., Park, Y. A., Choi, J. J., Do, I. G., et al. (2012). High galectin-1 expression correlates with poor prognosis and is involved in epithelial ovarian cancer proliferation and invasion. European Journal Cancer (in press)

  29. Saussez, S., Cucu, D. R., Decaestecker, C., Chevalier, D., Kaltner, H., Andre, S., et al. (2006). Galectin 7 (p53-induced gene 1): a new prognostic predictor of recurrence and survival in stage IV hypopharyngeal cancer. Annals of Surgical Oncology, 13(7), 999–1009.

    PubMed  Google Scholar 

  30. Perillo, N. L., Pace, K. E., Seilhamer, J. J., & Baum, L. G. (1995). Apoptosis of T cells mediated by galectin-1. Nature, 378(6558), 736–739.

    PubMed  CAS  Google Scholar 

  31. Rubinstein, N., Ilarregui, J. M., Toscano, M. A., & Rabinovich, G. A. (2004). The role of galectins in the initiation, amplification and resolution of the inflammatory response. Tissue Antigens, 64(1), 1–12.

    PubMed  CAS  Google Scholar 

  32. Grigorian, A., Torossian, S., & Demetriou, M. (2009). T-cell growth, cell surface organization, and the galectin-glycoprotein lattice. Immunology Reviews, 230(1), 232–246.

    CAS  Google Scholar 

  33. Nguyen, J. T., Evans, D. P., Galvan, M., Pace, K. E., Leitenberg, D., Bui, T. N., et al. (2001). CD45 modulates galectin-1-induced T cell death: regulation by expression of core 2 O-glycans. The Journal of Immunology, 167(10), 5697–5707.

    PubMed  CAS  Google Scholar 

  34. Pace, K. E., Hahn, H. P., Pang, M., Nguyen, J. T., & Baum, L. G. (2000). CD7 delivers a pro-apoptotic signal during galectin-1-induced T cell death. The Journal of Immunology, 165(5), 2331–2334.

    PubMed  CAS  Google Scholar 

  35. Hernandez, J. D., Nguyen, J. T., He, J., Wang, W., Ardman, B., Green, J. M., et al. (2006). Galectin-1 binds different CD43 glycoforms to cluster CD43 and regulate T cell death. The Journal of Immunology, 177(8), 5328–5336.

    PubMed  CAS  Google Scholar 

  36. Lange, F., Brandt, B., Tiedge, M., Jonas, L., Jeschke, U., Pohland, R., et al. (2009). Galectin-1 induced activation of the mitochondrial apoptotic pathway: evidence for a connection between death-receptor and mitochondrial pathways in human Jurkat T lymphocytes. Histochemistry and Cell Biology, 132(2), 211–223.

    PubMed  CAS  Google Scholar 

  37. Brandt, B., Abou-Eladab, E. F., Tiedge, M., & Walzel, H. (2010). Role of the JNK/c-Jun/AP-1 signaling pathway in galectin-1-induced T-cell death. Cell Death Diseases, 1, e23.

    CAS  Google Scholar 

  38. Vespa, G. N., Lewis, L. A., Kozak, K. R., Moran, M., Nguyen, J. T., Baum, L. G., et al. (1999). Galectin-1 specifically modulates TCR signals to enhance TCR apoptosis but inhibit IL-2 production and proliferation. The Journal of Immunology, 162(2), 799–806.

    PubMed  CAS  Google Scholar 

  39. Chung, C. D., Patel, V. P., Moran, M., Lewis, L. A., & Miceli, M. C. (2000). Galectin-1 induces partial TCR zeta-chain phosphorylation and antagonizes processive TCR signal transduction. The Journal of Immunology, 165(7), 3722–3729.

    PubMed  CAS  Google Scholar 

  40. Matarrese, P., Tinari, A., Mormone, E., Bianco, G. A., Toscano, M. A., Ascione, B., et al. (2005). Galectin-1 sensitizes resting human T lymphocytes to Fas (CD95)-mediated cell death via mitochondrial hyperpolarization, budding, and fission. The Journal of Biological Chemistry, 280(8), 6969–6985.

    PubMed  CAS  Google Scholar 

  41. Sturm, A., Lensch, M., Andre, S., Kaltner, H., Wiedenmann, B., Rosewicz, S., et al. (2004). Human galectin-2: novel inducer of T cell apoptosis with distinct profile of caspase activation. The Journal of Immunology, 173(6), 3825–3837.

    PubMed  CAS  Google Scholar 

  42. Hahn, H. P., Pang, M., He, J., Hernandez, J. D., Yang, R. Y., Li, L. Y., et al. (2004). Galectin-1 induces nuclear translocation of endonuclease G in caspase- and cytochrome c-independent T cell death. Cell Death and Differentiation, 11(12), 1277–1286.

    PubMed  CAS  Google Scholar 

  43. Yang, R. Y., Hsu, D. K., & Liu, F. T. (1996). Expression of galectin-3 modulates T-cell growth and apoptosis. Proceedings of the National Academy of Sciences of the United States of America, 93(13), 6737–6742.

    PubMed  CAS  Google Scholar 

  44. Fukumori, T., Takenaka, Y., Yoshii, T., Kim, H. R., Hogan, V., Inohara, H., et al. (2003). CD29 and CD7 mediate galectin-3-induced type II T-cell apoptosis. Cancer Research, 63(23), 8302–8311.

    PubMed  CAS  Google Scholar 

  45. Amano, M., Galvan, M., He, J., & Baum, L. G. (2003). The ST6Gal I sialyltransferase selectively modifies N-glycans on CD45 to negatively regulate galectin-1-induced CD45 clustering, phosphatase modulation, and T cell death. The Journal of Biological Chemistry, 278(9), 7469–7475.

    PubMed  CAS  Google Scholar 

  46. Lau, K. S., Partridge, E. A., Grigorian, A., Silvescu, C. I., Reinhold, V. N., Demetriou, M., et al. (2007). Complex N-glycan number and degree of branching cooperate to regulate cell proliferation and differentiation. Cell, 129(1), 123–134.

    PubMed  CAS  Google Scholar 

  47. Juszczynski, P., Ouyang, J., Monti, S., Rodig, S. J., Takeyama, K., Abramson, J., et al. (2007). The AP1-dependent secretion of galectin-1 by Reed Sternberg cells fosters immune privilege in classical Hodgkin lymphoma. Proceedings of the National Academy of Sciences of the United States of America, 104(32), 13134–13139.

    PubMed  CAS  Google Scholar 

  48. Toscano, M. A., Bianco, G. A., Ilarregui, J. M., Croci, D. O., Correale, J., Hernandez, J. D., et al. (2007). Differential glycosylation of TH1, TH2 and TH-17 effector cells selectively regulates susceptibility to cell death. Nature Immunology, 8(8), 825–834.

    PubMed  CAS  Google Scholar 

  49. Toscano, M. A., Commodaro, A. G., Ilarregui, J. M., Bianco, G. A., Liberman, A., Serra, H. M., et al. (2006). Galectin-1 suppresses autoimmune retinal disease by promoting concomitant Th2- and T regulatory-mediated anti-inflammatory responses. The Journal of Immunology, 176(10), 6323–6332.

    PubMed  CAS  Google Scholar 

  50. Harrington, L. E., Galvan, M., Baum, L. G., Altman, J. D., & Ahmed, R. (2000). Differentiating between memory and effector CD8 T cells by altered expression of cell surface O-glycans. The Journal of Experimental Medicine, 191(7), 1241–1246.

    PubMed  CAS  Google Scholar 

  51. Galvan, M., Tsuboi, S., Fukuda, M., & Baum, L. G. (2000). Expression of a specific glycosyltransferase enzyme regulates T cell death mediated by galectin-1. The Journal of Biological Chemistry, 275(22), 16730–16737.

    PubMed  CAS  Google Scholar 

  52. Ito, K., Scott, S. A., Cutler, S., Dong, L. F., Neuzil, J., Blanchard, H., et al. (2011). Thiodigalactoside inhibits murine cancers by concurrently blocking effects of galectin-1 on immune dysregulation, angiogenesis and protection against oxidative stress. [Research Support, Non-U.S. Gov't]. Angiogenesis, 14(3), 293–307.

    PubMed  CAS  Google Scholar 

  53. Banh, A., Zhang, J., Cao, H., Bouley, D. M., Kwok, S., Kong, C., et al. (2011). Tumor Galectin-1 mediates tumor growth and metastasis through regulation of T-cell apoptosis. Cancer Research, 71(13), 4423–4431.

    PubMed  CAS  Google Scholar 

  54. Hamzah, J., Jugold, M., Kiessling, F., Rigby, P., Manzur, M., Marti, H. H., et al. (2008). Vascular normalization in Rgs5-deficient tumours promotes immune destruction. Nature, 453(7193), 410–414.

    PubMed  CAS  Google Scholar 

  55. Goel, S., Duda, D. G., Xu, L., Munn, L. L., Boucher, Y., Fukumura, D., et al. (2011). Normalization of the vasculature for treatment of cancer and other diseases. Physiological Reviews, 91(3), 1071–1121.

    PubMed  CAS  Google Scholar 

  56. Shrimali, R. K., Yu, Z., Theoret, M. R., Chinnasamy, D., Restifo, N. P., & Rosenberg, S. A. (2010). Antiangiogenic agents can increase lymphocyte infiltration into tumor and enhance the effectiveness of adoptive immunotherapy of cancer. Cancer Research, 70(15), 6171–6180.

    PubMed  CAS  Google Scholar 

  57. Griffioen, A. W., & Molema, G. (2000). Angiogenesis: potentials for pharmacologic intervention in the treatment of cancer, cardiovascular diseases, and chronic inflammation. Pharmacological Reviews, 52(2), 237–268.

    PubMed  CAS  Google Scholar 

  58. Tozer, G. M., Kanthou, C., & Baguley, B. C. (2005). Disrupting tumour blood vessels. Nature Reviews Cancer, 5(6), 423–435.

    PubMed  CAS  Google Scholar 

  59. Castermans, K., & Griffioen, A. W. (2007). Tumor blood vessels, a difficult hurdle for infiltrating leukocytes. Biochimica et Biophysica Acta, 1776(2), 160–174.

    PubMed  CAS  Google Scholar 

  60. Thijssen, V. L., Hulsmans, S., & Griffioen, A. W. (2008). The galectin profile of the endothelium: altered expression and localization in activated and tumor endothelial cells. The American Journal of Pathology, 172(2), 545–553.

    PubMed  CAS  Google Scholar 

  61. Thijssen, V. L., Barkan, B., Shoji, H., Aries, I. M., Mathieu, V., Deltour, L., et al. (2010). Tumor cells secrete galectin-1 to enhance endothelial cell activity. Cancer Research, 70(15), 6216–6224.

    PubMed  CAS  Google Scholar 

  62. Le Mercier, M., Fortin, S., Mathieu, V., Roland, I., Spiegl-Kreinecker, S., Haibe-Kains, B., et al. (2009). Galectin 1 proangiogenic and promigratory effects in the Hs683 oligodendroglioma model are partly mediated through the control of BEX2 expression. Neoplasia, 11(5), 485–496.

    PubMed  Google Scholar 

  63. van den Brule, F., Califice, S., Garnier, F., Fernandez, P. L., Berchuck, A., & Castronovo, V. (2003). Galectin-1 accumulation in the ovary carcinoma peritumoral stroma is induced by ovary carcinoma cells and affects both cancer cell proliferation and adhesion to laminin-1 and fibronectin. Laboratory Investigation, 83(3), 377–386.

    PubMed  Google Scholar 

  64. Kawano, T., Takasaki, S., Tao, T. W., & Kobata, A. (1993). Altered glycosylation of beta 1 integrins associated with reduced adhesiveness to fibronectin and laminin. International Journal of Cancer, 53(1), 91–96.

    CAS  Google Scholar 

  65. Shintani, Y., Takashima, S., Asano, Y., Kato, H., Liao, Y., Yamazaki, S., et al. (2006). Glycosaminoglycan modification of neuropilin-1 modulates VEGFR2 signaling. The EMBO Journal, 25(13), 3045–3055.

    PubMed  CAS  Google Scholar 

  66. Pellet-Many, C., Frankel, P., Evans, I. M., Herzog, B., Junemann-Ramirez, M., & Zachary, I. C. (2011). Neuropilin-1 mediates PDGF stimulation of vascular smooth muscle cell migration and signalling via p130Cas. The Biochemical Journal, 435(3), 609–618.

    PubMed  CAS  Google Scholar 

  67. Hsieh, S. H., Ying, N. W., Wu, M. H., Chiang, W. F., Hsu, C. L., Wong, T. Y., et al. (2008). Galectin-1, a novel ligand of neuropilin-1, activates VEGFR-2 signaling and modulates the migration of vascular endothelial cells. Oncogene, 27(26), 3746–3753.

    PubMed  CAS  Google Scholar 

  68. Sugahara, K. N., Teesalu, T., Karmali, P. P., Kotamraju, V. R., Agemy, L., Greenwald, D. R., et al. (2010). Coadministration of a tumor-penetrating peptide enhances the efficacy of cancer drugs. Science, 328(5981), 1031–1035.

    PubMed  CAS  Google Scholar 

  69. Semenza, G. L. (2007). Hypoxia and cancer. Cancer and Metastasis Reviews, 26(2), 223–224.

    PubMed  CAS  Google Scholar 

  70. Brown, N. S., & Bicknell, R. (2001). Hypoxia and oxidative stress in breast cancer. Oxidative stress: its effects on the growth, metastatic potential and response to therapy of breast cancer. Breast Cancer Research, 3(5), 323–327.

    PubMed  CAS  Google Scholar 

  71. Matsumoto, S., Yasui, H., Mitchell, J. B., & Krishna, M. C. (2010). Imaging cycling tumor hypoxia. Cancer Research, 70(24), 10019–10023.

    PubMed  CAS  Google Scholar 

  72. Martinive, P., Defresne, F., Bouzin, C., Saliez, J., Lair, F., Grégoire, V., et al. (2006). Preconditioning of the tumor vasculature and tumor cells by intermittent hypoxia: implications for anticancer therapies. Cancer Research, 66(24), 11736–11744.

    PubMed  CAS  Google Scholar 

  73. Dewhirst, M. W., Cao, Y., & Moeller, B. (2008). Cycling hypoxia and free radicals regulate angiogenesis and radiotherapy response. Nature Reviews Cancer, 8(6), 425–437.

    PubMed  CAS  Google Scholar 

  74. Vaupel, P. (2008). Hypoxia and aggressive tumor phenotype: implications for therapy and prognosis. The Oncologist, 13(Suppl 3), 21–26.

    PubMed  CAS  Google Scholar 

  75. Palazon, A., Aragones Lopez, J., Morales-Kastresana, A., Ortiz Del Landazuri, M., & Melero, I. J. (2012). Molecular pathways: hypoxia response in immune cells fighting or promoting cancer. Clin Cancer Res, 18, 1207–1213.

    PubMed  CAS  Google Scholar 

  76. Lukashev, D., Klebanov, B., Kojima, H., Grinberg, A., Ohta, A., Berenfeld, L., et al. (2006). Cutting edge: hypoxia-inducible factor 1alpha and its activation-inducible short isoform I.1 negatively regulate functions of CD4+ and CD8+ T lymphocytes. The Journal of Immunology, 177(8), 4962–4965.

    PubMed  CAS  Google Scholar 

  77. Noman, M. Z., Buart, S., Van Pelt, J., Richon, C., Hasmim, M., Leleu, N., et al. (2009). The cooperative induction of hypoxia-inducible factor-1 alpha and STAT3 during hypoxia induced an impairment of tumor susceptibility to CTL-mediated cell lysis. The Journal of Immunology, 182(6), 3510–3521.

    PubMed  CAS  Google Scholar 

  78. Eltzschig, H. K., Thompson, L. F., Karhausen, J., Cotta, R. J., Ibla, J. C., Robson, S. C., et al. (2004). Endogenous adenosine produced during hypoxia attenuates neutrophil accumulation: coordination by extracellular nucleotide metabolism. Blood, 104(13), 3986–3992.

    PubMed  CAS  Google Scholar 

  79. Ohta, A., Gorelik, E., Prasad, S. J., Ronchese, F., Lukashev, D., Wong, M. K., et al. (2006). A2A adenosine receptor protects tumors from antitumor T cells. Proceedings of the National Academy of Sciences of the United States of America, 103(35), 13132–13137.

    PubMed  CAS  Google Scholar 

  80. Facciabene, A., Peng, X., Hagemann, I. S., Balint, K., Barchetti, A., Wang, L. P., et al. (2011). Tumour hypoxia promotes tolerance and angiogenesis via CCL28 and T(reg) cells. Nature, 475(7355), 226–230.

    PubMed  CAS  Google Scholar 

  81. Zhao, X. Y., Chen, T. T., Xia, L., Guo, M., Xu, Y., Yue, F., et al. (2010). Hypoxia inducible factor-1 mediates expression of galectin-1: the potential role in migration/invasion of colorectal cancer cells. Carcinogenesis, 31(8), 1367–1375.

    PubMed  CAS  Google Scholar 

  82. Le, Q. T., Shi, G., Cao, H., Nelson, D. W., Wang, Y., Chen, E. Y., et al. (2005). Galectin-1: a link between tumor hypoxia and tumor immune privilege. Journal of Clinical Oncology, 23(35), 8932–8941.

    PubMed  CAS  Google Scholar 

  83. Olbryt, M., Habryka, A., Tyszkiewicz, T., Rusin, A., Cichon, T., Jarzab, M., et al. (2011). Melanoma-associated genes, MXI1, FN1, and NME1, are hypoxia responsive in murine and human melanoma cells. Melanoma Research, 21(5), 417–425.

    PubMed  CAS  Google Scholar 

  84. Gamrekelashvili, J., Kruger, C., von Wasielewski, R., Hoffmann, M., Huster, K. M., Busch, D. H., et al. (2007). Necrotic tumor cell death in vivo impairs tumor-specific immune responses. The Journal of Immunology, 178(3), 1573–1580.

    PubMed  CAS  Google Scholar 

  85. Iiizumi, M., Mohinta, S., Bandyopadhyay, S., & Watabe, K. (2007). Tumor-endothelial cell interactions: therapeutic potential. Microvascular Research, 74(2–3), 114–120.

    PubMed  CAS  Google Scholar 

  86. Miles, F. L., Pruitt, F. L., van Golen, K. L., & Cooper, C. R. (2008). Stepping out of the flow: capillary extravasation in cancer metastasis. Clinical & Experimental Metastasis, 25(4), 305–324.

    CAS  Google Scholar 

  87. van den Brule, F. A., Buicu, C., Baldet, M., Sobel, M. E., Cooper, D. N., Marschal, P., et al. (1995). Galectin-1 modulates human melanoma cell adhesion to laminin. Biochemical and Biophysical Research Communications, 209(2), 760–767.

    PubMed  Google Scholar 

  88. Perillo, N. L., Marcus, M. E., & Baum, L. G. (1998). Galectins: versatile modulators of cell adhesion, cell proliferation, and cell death. Journal Molecular Medica (Berliner), 76(6), 402–412.

    CAS  Google Scholar 

  89. Ito, K., & Ralph, S. J. (2012). Inhibiting galectin-1 reduces murine lung metastasis with increased CD4(+) and CD8 (+) T cells and reduced cancer cell adherence. Clinical and Experimental Metastasis. doi:10.1007/s10585-012-9471-7.

  90. Elola, M. T., Wolfenstein-Todel, C., Troncoso, M. F., Vasta, G. R., & Rabinovich, G. A. (2007). Galectins: matricellular glycan-binding proteins linking cell adhesion, migration, and survival. Cellular and Molecular Life Sciences, 64(13), 1679–1700.

    PubMed  CAS  Google Scholar 

  91. Ito, K., & Ralph, S. J. (2012). Inhibiting galectin-1 reduces murine lung metastasis with increased CD4+ and CD8+ T cells and reduced cancer cell adherence. Clinical and Experimental Metastasis.

  92. Kuo, P. L., Huang, M. S., Cheng, D. E., Hung, J. Y., Yang, C. J., & Chou, S. H. (2012). Lung cancer-derived galectin-1 enhances tumorigenic potentiation of tumor associated dendritic cells by expressing HB-EGF. Journal of Biological Chemistry, 23;287(13):9753–9764.

    Google Scholar 

  93. Huang, E. Y., Chen, Y. F., Chen, Y. M., Lin, I. H., Wang, C. C., Su, W. H., et al. (2012). A novel radioresistant mechanism of galectin-1 mediated by H-Ras-dependent pathways in cervical cancer cells. Cell Death Disease, 3, e251.

    PubMed  Google Scholar 

  94. Cho, H. J., Jeong, H. G., Lee, J. S., Woo, E. R., Hyun, J. W., Chung, M. H., et al. (2002). Oncogenic H-Ras enhances DNA repair through the Ras/phosphatidylinositol 3-kinase/Rac1 pathway in NIH3T3 cells. Evidence for association with reactive oxygen species. The Journal of Biological Chemistry, 277(22), 19358–19366.

    PubMed  CAS  Google Scholar 

  95. Hancock, J. F. (2003). Ras proteins: different signals from different locations. Nature Reviews Molecular Cell Biology, 4(5), 373–384.

    PubMed  CAS  Google Scholar 

  96. Rotblat, B., Niv, H., Andre, S., Kaltner, H., Gabius, H. J., & Kloog, Y. (2004). Galectin-1(L11A) predicted from a computed galectin-1 farnesyl-binding pocket selectively inhibits Ras-GTP. Cancer Research, 64(9), 3112–3118.

    PubMed  CAS  Google Scholar 

  97. Paz, A., Haklai, R., Elad-Sfadia, G., Ballan, E., & Kloog, Y. (2001). Galectin-1 binds oncogenic H-Ras to mediate Ras membrane anchorage and cell transformation. Oncogene, 20(51), 7486–7493.

    PubMed  CAS  Google Scholar 

  98. Cumpstey, I., Sundin, A., Leffler, H., & Nilsson, U. J. (2005). C2-symmetrical thiodigalactoside bis-benzamido derivatives as high-affinity inhibitors of galectin-3: efficient lectin inhibition through double arginine-arene interactions. Angewandte Chemie (International Ed. in English), 44(32), 5110–5112.

    CAS  Google Scholar 

  99. Cumpstey, I., Salomonsson, E., Sundin, A., Leffler, H., & Nilsson, U. J. (2007). Studies of arginine-arene interactions through synthesis and evaluation of a series of galectin-binding aromatic lactose esters. Chembiochem, 8(12), 1389–1398.

    PubMed  CAS  Google Scholar 

  100. Collins, P. M., Oberg, C. T., Leffler, H., Nilsson, U. J., & Blanchard, H. (2012). Taloside inhibitors of Galectin-1 and Galectin-3. Chemical Biology Drug Design, 79, 339–346.

    PubMed  CAS  Google Scholar 

  101. Brandwijk, R. J., Dings, R. P., van der Linden, E., Mayo, K. H., Thijssen, V. L., & Griffioen, A. W. (2006). Anti-angiogenesis and anti-tumor activity of recombinant anginex. Biochemical and Biophysical Research Communications, 349(3), 1073–1078.

    PubMed  CAS  Google Scholar 

  102. Brandwijk, R. J., Mulder, W. J., Nicolay, K., Mayo, K. H., Thijssen, V. L., & Griffioen, A. W. (2007). Anginex-conjugated liposomes for targeting of angiogenic endothelial cells. Bioconjugate Chemistry, 18(3), 785–790.

    PubMed  CAS  Google Scholar 

  103. Griffioen, A. W., van der Schaft, D. W., Barendsz-Janson, A. F., Cox, A., Struijker Boudier, H. A., Hillen, H. F., et al. (2001). Anginex, a designed peptide that inhibits angiogenesis. The Biochemical Journal, 354(Pt 2), 233–242.

    PubMed  CAS  Google Scholar 

  104. Dings, R. P., van der Schaft, D. W., Hargittai, B., Haseman, J., Griffioen, A. W., & Mayo, K. H. (2003). Anti-tumor activity of the novel angiogenesis inhibitor anginex. Cancer Letters, 194(1), 55–66.

    PubMed  CAS  Google Scholar 

  105. Salomonsson, E., Thijssen, V. L., Griffioen, A. W., Nilsson, U. J., & Leffler, H. (2011). The anti-angiogenic peptide anginex greatly enhances galectin-1 binding affinity for glycoproteins. The Journal of Biological Chemistry, 286(16), 13801–13804.

    PubMed  CAS  Google Scholar 

  106. Pienta, K. J., Naik, H., Akhtar, A., Yamazaki, K., Replogle, T. S., Lehr, J., et al. (1995). Inhibition of spontaneous metastasis in a rat prostate cancer model by oral administration of modified citrus pectin. Journal of the National Cancer Institute, 87(5), 348–353.

    PubMed  CAS  Google Scholar 

  107. 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.

    PubMed  CAS  Google Scholar 

  108. Liu, H. Y., Huang, Z. L., Yang, G. H., Lu, W. Q., & Yu, N. R. (2008). Inhibitory effect of modified citrus pectin on liver metastases in a mouse colon cancer model. World Journal of Gastroenterology, 14(48), 7386–7391.

    PubMed  CAS  Google Scholar 

  109. Miller, M. C., Klyosov, A., & Mayo, K. H. (2011). Structural Features for alpha-galactomannan binding to galectin-1. Glycobiology

  110. Cedeno-Laurent, F., Opperman, M. J., Barthel, S. R., Hays, D., Schatton, T., Zhan, Q., et al. (2012). Metabolic inhibition of galectin-1-binding carbohydrates accentuates antitumor immunity. Journal Investment Dermatology, 132, 410–420.

    CAS  Google Scholar 

  111. Hirabayashi, J., Hashidate, T., Arata, Y., Nishi, N., Nakamura, T., Hirashima, M., et al. (2002). Oligosaccharide specificity of galectins: a search by frontal affinity chromatography. Biochimica et Biophysica Acta, 1572(2–3), 232–254.

    PubMed  CAS  Google Scholar 

  112. Pace, K. E., Lee, C., Stewart, P. L., & Baum, L. G. (1999). Restricted receptor segregation into membrane microdomains occurs on human T cells during apoptosis induced by galectin-1. The Journal of Immunology, 163(7), 3801–3811.

    PubMed  CAS  Google Scholar 

  113. Lau, K. S., & Dennis, J. W. (2008). N-Glycans in cancer progression. Glycobiology, 18(10), 750–760.

    PubMed  CAS  Google Scholar 

  114. Lange, T., Ullrich, S., Müller, I., Nentwich, M. F., Stübke, K., Feldhaus, S., et al. (2012). Human prostate cancer in a clinically relevant xenograft mouse model: identification of β(1,6)-branched oligosaccharides as a marker of tumor progression. Clinical Cancer Research, 18(5), 1–10.

    Google Scholar 

  115. Wong, C. S., Sceneay, J. E., House, C. M., Halse, H. M., Liu, M. C., George, J., et al. (2012). Vascular normalization by loss of Siah2-/- results in increased chemotherapeutic efficacy. Cancer Research, 72, 1694–1704.

    PubMed  CAS  Google Scholar 

  116. Amano, M., Suzuki, M., Andoh, S., Monzen, H., Terai, K., Williams, B., et al. (2007). Antiangiogenesis therapy using a novel angiogenesis inhibitor, anginex, following radiation causes tumor growth delay. International Journal of Clinical Oncology, 12(1), 42–47.

    PubMed  Google Scholar 

  117. Dings, R. P., Yokoyama, Y., Ramakrishnan, S., Griffioen, A. W., & Mayo, K. H. (2003). The designed angiostatic peptide anginex synergistically improves chemotherapy and antiangiogenesis therapy with angiostatin. Cancer Research, 63(2), 382–385.

    PubMed  CAS  Google Scholar 

  118. Dings, R. P., Van Laar, E. S., Loren, M., Webber, J., Zhang, Y., Waters, S. J., et al. (2010). Inhibiting tumor growth by targeting tumor vasculature with galectin-1 antagonist anginex conjugated to the cytotoxic acylfulvene, 6-hydroxylpropylacylfulvene. Bioconjugate Chemistry, 21(1), 20–27.

    PubMed  CAS  Google Scholar 

  119. He, J., & Baum, L. G. (2006). Endothelial cell expression of galectin-1 induced by prostate cancer cells inhibits T-cell transendothelial migration. Laboratory Investigation, 86(6), 578–590.

    PubMed  CAS  Google Scholar 

  120. Stannard, K. A., Collins, P. M., Ito, K., Sullivan, E. M., Scott, S. A., Gabutero, E., et al. (2010). Galectin inhibitory disaccharides promote tumour immunity in a breast cancer model. Cancer Letters, 299(2), 95–110.

    PubMed  CAS  Google Scholar 

  121. Lahm, H., Andre, S., Hoeflich, A., Fischer, J. R., Sordat, B., Kaltner, H., et al. (2001). Comprehensive galectin fingerprinting in a panel of 61 human tumor cell lines by RT-PCR and its implications for diagnostic and therapeutic procedures. Journal of Cancer Research and Clinical Oncology, 127(6), 375–386.

    PubMed  CAS  Google Scholar 

  122. Kageshita, T., Kashio, Y., Yamauchi, A., Seki, M., Abedin, M. J., Nishi, N., et al. (2002). Possible role of galectin-9 in cell aggregation and apoptosis of human melanoma cell lines and its clinical significance. International Journal of Cancer, 99(6), 809–816.

    CAS  Google Scholar 

  123. Mathieu, V., Le Mercier, M., De Neve, N., Sauvage, S., Gras, T., Roland, I., et al. (2007). Galectin-1 knockdown increases sensitivity to temozolomide in a B16F10 mouse metastatic melanoma model. The Journal of Investigative Dermatology, 127(10), 2399–2410.

    PubMed  CAS  Google Scholar 

  124. Le Mercier, M., Lefranc, F., Mijatovic, T., Debeir, O., Haibe-Kains, B., Bontempi, G., et al. (2008). Evidence of galectin-1 involvement in glioma chemoresistance. Toxicology and Applied Pharmacology, 229(2), 172–183.

    PubMed  Google Scholar 

  125. Alves, P. M., Godoy, G. P., Gomes, D. Q., Medeiros, A. M., de Souza, L. B., da Silveira, E. J., et al. (2011). Significance of galectins-1, -3, -4 and -7 in the progression of squamous cell carcinoma of the tongue. Pathology Research and Practice, 207(4), 236–240.

    CAS  Google Scholar 

  126. Rubinstein, N., Alvarez, M., Zwirner, N. W., Toscano, M. A., Ilarregui, J. M., Bravo, A., et al. (2004). Targeted inhibition of galectin-1 gene expression in tumor cells results in heightened T cell-mediated rejection; a potential mechanism of tumor-immune privilege. Cancer Cell, 5(3), 241–251.

    PubMed  CAS  Google Scholar 

  127. Cooper, D., Norling, L. V., & Perretti, M. (2008). Novel insights into the inhibitory effects of galectin-1 on neutrophil recruitment under flow. Journal of Leukocyte Biology, 83(6), 1459–1466.

    PubMed  CAS  Google Scholar 

  128. Iurisci, I., Tinari, N., Natoli, C., Angelucci, D., Cianchetti, E., & Iacobelli, S. (2000). Concentrations of galectin-3 in the sera of normal controls and cancer patients. Clinical Cancer Research, 6(4), 1389–1393.

    PubMed  CAS  Google Scholar 

  129. Paret, C., Hildebrand, D., Weitz, J., Kopp-Schneider, A., Kuhn, A., Beer, A., et al. (2007). C4.4A as a candidate marker in the diagnosis of colorectal cancer. British Journal of Cancer, 97(8), 1156.

    Google Scholar 

  130. Righi, A., Jin, L., Zhang, S., Stilling, G., Scheithauer, B. W., Kovacs, K., et al. (2010). Identification and consequences of galectin-3 expression in pituitary tumors. Molecular and Cellular Endocrinology, 326(1–2), 8–14.

    PubMed  CAS  Google Scholar 

  131. Nagy, N., Legendre, H., Engels, O., Andre, S., Kaltner, H., Wasano, K., et al. (2003). Refined prognostic evaluation in colon carcinoma using immunohistochemical galectin fingerprinting. Cancer, 97(8), 1849–1858.

    PubMed  Google Scholar 

  132. Kobayashi, T., Shimura, T., Yajima, T., Kubo, N., Araki, K., Tsutsumi, S., et al. (2011). Transient gene silencing of galectin-3 suppresses pancreatic cancer cell migration and invasion through degradation of beta-catenin. International Journal of Cancer, 129(12), 2775–2786.

    CAS  Google Scholar 

  133. Ahmed, H., Cappello, F., Rodolico, V., & Vasta, G. R. (2009). 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. Translational Oncology, 2(3), 146–156.

    PubMed  Google Scholar 

  134. van den Brule, F. A., Waltregny, D., Liu, F. T., & Castronovo, V. (2000). Alteration of the cytoplasmic/nuclear expression pattern of galectin-3 correlates with prostate carcinoma progression. International Journal of Cancer, 89(4), 361–367.

    Google Scholar 

  135. Peng, W., Wang, H. Y., Miyahara, Y., Peng, G., & Wang, R. F. (2008). Tumor-associated galectin-3 modulates the function of tumor-reactive T cells. Cancer Research, 68(17), 7228–7236.

    PubMed  CAS  Google Scholar 

  136. Endo, K., Kohnoe, S., Tsujita, E., Watanabe, A., Nakashima, H., Baba, H., et al. (2005). Galectin-3 expression is a potent prognostic marker in colorectal cancer. Anticancer Research, 25(4), 3117–3121.

    PubMed  CAS  Google Scholar 

  137. Kobayashi, T., Shimura, T., Yajima, T., Kubo, N., Araki, K., Wada, W., et al. (2011). Transient silencing of galectin-3 expression promotes both in vitro and in vivo drug-induced apoptosis of human pancreatic carcinoma cells. Clinical & Experimental Metastasis, 28(4), 367–376.

    CAS  Google Scholar 

  138. Cheong, T. C., Shin, J. Y., & Chun, K. H. (2010). Silencing of galectin-3 changes the gene expression and augments the sensitivity of gastric cancer cells to chemotherapeutic agents. Cancer Science, 101(1), 94–102.

    PubMed  CAS  Google Scholar 

  139. Merseburger, A. S., Kramer, M. W., Hennenlotter, J., Simon, P., Knapp, J., Hartmann, J. T., et al. (2008). Involvement of decreased galectin-3 expression in the pathogenesis and progression of prostate cancer. The Prostate, 68(1), 72–77.

    PubMed  Google Scholar 

  140. Pacis, R. A., Pilat, M. J., Pienta, K. J., Wojno, K., Raz, A., Hogan, V., et al. (2000). Decreased galectin-3 expression in prostate cancer. The Prostate, 44(2), 118–123.

    PubMed  CAS  Google Scholar 

  141. Wang, Y. G., Kim, S. J., Baek, J. H., Lee, H. W., Jeong, S. Y., & Chun, K. H. (2012). Galectin-3 increases the motility of mouse melanoma cells by regulating MMP-1 expression. Experimental & Molecular Medicine (in press)

  142. Heinzelmann-Schwarz, V. A., Gardiner-Garden, M., Henshall, S. M., Scurry, J. P., Scolyer, R. A., Smith, A. N., et al. (2006). A distinct molecular profile associated with mucinous epithelial ovarian cancer. British Journal of Cancer, 94(6), 904–913.

    PubMed  CAS  Google Scholar 

  143. Heinzelmann-Schwarz, V. A., Scolyer, R. A., Scurry, J. P., Smith, A. N., Gardiner-Garden, M., Biankin, A. V., et al. (2007). Low meprin alpha expression differentiates primary ovarian mucinous carcinoma from gastrointestinal cancers that commonly metastasise to the ovaries. Journal of Clinical Pathology, 60(6), 622–626.

    PubMed  CAS  Google Scholar 

  144. Demers, M., Biron-Pain, K., Hebert, J., Lamarre, A., Magnaldo, T., & St-Pierre, Y. (2007). Galectin-7 in lymphoma: elevated expression in human lymphoid malignancies and decreased lymphoma dissemination by antisense strategies in experimental model. Cancer Research, 67(6), 2824–2829.

    PubMed  CAS  Google Scholar 

  145. Moisan, S., Demers, M., Mercier, J., Magnaldo, T., Potworowski, E. F., & St-Pierre, Y. (2003). Upregulation of galectin-7 in murine lymphoma cells is associated with progression toward an aggressive phenotype. Leukemia, 17(4), 751–759.

    PubMed  CAS  Google Scholar 

  146. Liang, X. Q., Cao, E. H., Zhang, Y., & Qin, J. F. (2003). P53-induced gene 11 (PIG11) involved in arsenic trioxide-induced apoptosis in human gastric cancer MGC-803 cells. Oncology Reports, 10(5), 1265–1269.

    PubMed  CAS  Google Scholar 

  147. Nagy, N., Bronckart, Y., Camby, I., Legendre, H., Lahm, H., Kaltner, H., et al. (2002). Galectin-8 expression decreases in cancer compared with normal and dysplastic human colon tissue and acts significantly on human colon cancer cell migration as a suppressor. Gut, 50(3), 392–401.

    PubMed  CAS  Google Scholar 

  148. Klibi, J., Niki, T., Riedel, A., Pioche-Durieu, C., Souquere, S., Rubinstein, E., et al. (2009). Blood diffusion and Th1-suppressive effects of galectin-9-containing exosomes released by Epstein-Barr virus-infected nasopharyngeal carcinoma cells. Blood, 113(9), 1957–1966.

    PubMed  CAS  Google Scholar 

  149. Yamauchi, A., Kontani, K., Kihara, M., Nishi, N., Yokomise, H., & Hirashima, M. (2006). Galectin-9, a novel prognostic factor with antimetastatic potential in breast cancer. The Breast Journal, 12(5 Suppl 2), S196–S200.

    PubMed  Google Scholar 

  150. Irie, A., Yamauchi, A., Kontani, K., Kihara, M., Liu, D., Shirato, Y., et al. (2005). Galectin-9 as a prognostic factor with antimetastatic potential in breast cancer. Clinical Cancer Research, 11(8), 2962–2968.

    PubMed  CAS  Google Scholar 

  151. Yang, R. Y., Hsu, D. K., Yu, L., Ni, J., & Liu, F. T. (2001). Cell cycle regulation by galectin-12, a new member of the galectin superfamily. The Journal of Biological Chemistry, 276(23), 20252–20260.

    PubMed  CAS  Google Scholar 

  152. Barthel, S. R., Antonopoulos, A., Cedeno-Laurent, F., Schaffer, L., Hernandez, G., Patil, S. A., et al. (2011). Peracetylated 4-fluoro-glucosamine reduces the content and repertoire of N- and O-glycans without direct incorporation. The Journal of Biological Chemistry, 286(24), 21717–21731.

    PubMed  CAS  Google Scholar 

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Acknowledgments

We thank Dr. Lan-feng Dong and Dr. Stacy Scott for their help and advice on the galectin-1 studies. The study was supported by grant funding from the Cancer Council Queensland, Australia.

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Authors and Affiliations

  1. School of Medical Science, Griffith Health Institute, Griffith University, Parklands Drive, Southport, Queensland, 4222, Australia

    Koichi Ito, Kimberley Stannard, Elwyn Gabutero, Amanda M. Clark, Selda Onturk & Stephen J. Ralph

  2. Centre for Immune and Target Therapies, Gallipoli Medical Research Foundation, Greenslopes Private Hospital, Greenslopes, Queensland, 4120, Australia

    Kimberley Stannard

  3. School of Chemical and Life Sciences, Singapore Polytechnic, 500 Dover Road, Singapore, Singapore

    Shi-Yong Neo

  4. Institute for Glycomics, Griffith University, Parklands Drive, Southport, Queensland, 4222, Australia

    Koichi Ito & Helen Blanchard

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  1. Koichi Ito
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Ito, K., Stannard, K., Gabutero, E. et al. Galectin-1 as a potent target for cancer therapy: role in the tumor microenvironment. Cancer Metastasis Rev 31, 763–778 (2012). https://doi.org/10.1007/s10555-012-9388-2

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