Advertisement

Galectins pp 293-304 | Cite as

Regulation of Galectins by Hypoxia and Their Relevance in Angiogenesis: Strategies and Methods

  • Mariana SalatinoEmail author
  • Diego O. Croci
  • Diego J. Laderach
  • Daniel Compagno
  • Lucas Gentilini
  • Tomas Dalotto-Moreno
  • L. Sebastián Dergan-Dylon
  • Santiago P. Méndez-Huergo
  • Marta A. Toscano
  • Juan P. Cerliani
  • Gabriel A. Rabinovich
Part of the Methods in Molecular Biology book series (MIMB, volume 1207)

Abstract

Formation of an aberrant and heterogeneous vascular network is a key pathological event in the multistep process of tumor growth and metastasis. Pro-angiogenic factors are synthesized and released from tumor, stromal, endothelial, and myeloid cells in response to hypoxic and immunosuppressive microenvironments which are commonly found during cancer progression. Emerging data indicate key roles for galectins, particularly galectin-1, -3, -8, and -9 in the regulation of angiogenesis in different pathophysiologic settings. Each galectin interacts with a preferred set of glycosylated receptors, triggers different signaling pathway, and promotes sprouting angiogenesis through different mechanisms. Understanding the role of galectins in tumor neovascularization will contribute to the design of novel anti-angiogenic therapies aimed at complementing current clinical approaches. Here we describe selected strategies and methods used to study the galectin-1 regulation by hypoxia and its role in blood vessel formation.

Key words

Galectin Angiogenesis Tumor neovascularization Hypoxia 

Notes

Acknowledgements

Work in our laboratory is supported by grants from Argentinean Agency for Promotion of Science and Technology (G.A.R, M.S., D.J.L, M.A.T), University of Buenos Aires (G.A.R), Prostate Cancer Action (G.A.R., D.J.L, D.C), Argentinean Council of Scientific and Technical Investigations (M.S), National Multiple Sclerosis Society (G.A.R.), Broad Foundation (G.A.R.), and Sales Foundation (G.A.R).

References

  1. 1.
    Ferrara N, Alitalo K (1999) Clinical applications of angiogenic growth factors and their inhibitors. Nat Med 5:1359–1364PubMedCrossRefGoogle Scholar
  2. 2.
    Carmeliet P, Jain RK (2000) Angiogenesis in cancer and other diseases. Nature 407:249–257PubMedCrossRefGoogle Scholar
  3. 3.
    Croci D et al (2012) Disrupting galectin-1 interactions with Nglycans suppresses hypoxia-driven angiogenesis and tumorigenesis in Kaposi’s sarcoma. J Exp Med 209(11):1985–2000PubMedCrossRefPubMedCentralGoogle Scholar
  4. 4.
    Le QT et al (2005) Galectin-1: a link between tumor hypoxia and tumor immune privilege. J Clin Oncol 23:8932–8941PubMedCrossRefGoogle Scholar
  5. 5.
    Zhao XY, Zhao KW, Jiang Y, Zhao M, Chen GQ (2011) Synergistic induction of galectin-1 by CCAAT/enhancer binding protein alpha and hypoxia-inducible factor 1alpha and its role in differentiation of acute myeloid leukemic cells. J Biol Chem 286:36808–36819PubMedCrossRefPubMedCentralGoogle Scholar
  6. 6.
    Thijssen VL et al (2010) Tumor cells secrete galectin-1 to enhance endothelial cell activity. Cancer Res 70:6216–6224PubMedCrossRefGoogle Scholar
  7. 7.
    Thijssen VL et al (2006) Galectin-1 is essential in tumor angiogenesis and is a target for antiangiogenesis therapy. Proc Natl Acad Sci U S A 103:15975–15980PubMedCrossRefPubMedCentralGoogle Scholar
  8. 8.
    Hsieh SH et al (2008) Galectin-1, a novel ligand of neuropilin-1, activates VEGFR-2 signaling and modulates the migration of vascular endothelial cells. Oncogene 27:3746–3753PubMedCrossRefGoogle Scholar
  9. 9.
    Mathieu V et al (2012) Galectin-1 in melanoma biology and related neo-angiogenesis processes. J Invest Dermatol 132:2245–2254PubMedCrossRefGoogle Scholar
  10. 10.
    Laderach DJ et al (2013) A unique galectin signature in human prostate cancer progression suggests galectin-1 as a key target for treatment of advanced disease. Cancer Res 73:86–96PubMedCrossRefGoogle Scholar
  11. 11.
    Markowska AI, Liu FT, Panjwani N (2010) Galectin-3 is an important mediator of VEGF- and bFGF-mediated angiogenic response. J Exp Med 207:1981–1993PubMedCrossRefPubMedCentralGoogle Scholar
  12. 12.
    Markowska AI, Jefferies KC, Panjwani N (2011) Galectin-3 protein modulates cell surface expression and activation of vascular endothelial growth factor receptor 2 in human endothelial cells. J Biol Chem 286:29913–29921PubMedCrossRefPubMedCentralGoogle Scholar
  13. 13.
    Nangia-Makker P, Balan V, Raz A (2008) Regulation of tumor progression by extracellular galectin-3. Cancer Microenviron 1:43–51PubMedCrossRefPubMedCentralGoogle Scholar
  14. 14.
    Delgado VM et al (2011) Modulation of endothelial cell migration and angiogenesis: a novel function for the “tandem-repeat” lectin galectin-8. FASEB J 25:242–254PubMedCrossRefGoogle Scholar
  15. 15.
    Croci DO et al. (2014) Glycosylation-dependent lectin-receptor interactions preserve angiogenesis in anti-VEGF refractory tumors. Cell 156:744–58PubMedCrossRefGoogle Scholar
  16. 16.
    Croci DO et al (2011) Fucans, but not fucomannoglucuronans, determine the biological activities of sulfated polysaccharides from Laminaria saccharina brown seaweed. PLoS ONE 6:e17283PubMedCrossRefPubMedCentralGoogle Scholar
  17. 17.
    Toscano MA et al (2007) Dissecting the pathophysiologic role of endogenous lectins: glycan-binding proteins with cytokine-like activity? Cytokine Growth Factor Rev 18:57–71PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Mariana Salatino
    • 1
    Email author
  • Diego O. Croci
    • 1
  • Diego J. Laderach
    • 2
  • Daniel Compagno
    • 2
  • Lucas Gentilini
    • 2
  • Tomas Dalotto-Moreno
    • 1
  • L. Sebastián Dergan-Dylon
    • 1
  • Santiago P. Méndez-Huergo
    • 1
  • Marta A. Toscano
    • 1
  • Juan P. Cerliani
    • 1
  • Gabriel A. Rabinovich
    • 3
  1. 1.Laboratorio de Inmunopatología, Instituto de Biología y Medicina Experimental (IBYME)Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET)Buenos AiresArgentina
  2. 2.Laboratorio de Glicómica Funcional, Departamento de Química Biológica, Facultad de Ciencias Exactas y NaturalesUniversidad de Buenos AiresBuenos AiresArgentina
  3. 3.Laboratorio de Glicómica Funcional, Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales and Laboratorio de Inmunopatología, Instituto de Biología y Medicina Experimental (IBYME)Universidad de Buenos Aires and Consejo Nacional de Investigaciones Científicasy Técnicas (CONICET)Buenos AiresArgentina

Personalised recommendations