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Galectins as modulators of tumour progression

Nature Reviews Cancer volume 5, pages 29–41 (2005)Cite this article

Key Points

  • Galectins are a family of animal lectins that have affinity for β-galactosides and that share similar amino-acid sequences.

  • Galectins bind to a wide array of glycoproteins and glycolipids both on the cell surface and in extracellular matrices.

  • By binding to these glycoconjugates, galectins deliver signals intracellularly as well as mediate cell–cell and cell–extracellular matrix adhesion.

  • The most extensively-studied function of galectins is the regulation of apoptosis; some galectins can induce apoptosis when added exogenously to cells, whereas others regulate apoptosis through intracellular mechanisms.

  • Galectin-1 and galectin-3 can interact with oncogenic Ras and mediate cell transformation induced by this oncogene.

  • Galectins can modulate cell adhesion and cell migration, thereby affecting the process of tumour metastasis.

  • Galectin-3 has angiogenic activity.

  • Galectins have pro- and anti-inflammatory functions and modulate the immune response. Furthermore, galectin-1 functions as a soluble mediator employed by tumour cells to evade the immune response.

Abstract

Galectins are a family of animal lectins with diverse biological activities. They function both extracellularly, by interacting with cell-surface and extracellular matrix glycoproteins and glycolipids, and intracellularly, by interacting with cytoplasmic and nuclear proteins to modulate signalling pathways. Current research indicates that galectins have important roles in cancer; they contribute to neoplastic transformation, tumour cell survival, angiogenesis and tumour metastasis. They can modulate the immune and inflammatory responses and might have a key role helping tumours to escape immune surveillance. How do the different members of the Galectin family contribute to these diverse aspects of tumour biology?

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Figure 1: The Galectin family.
Figure 2: Intracellular and extracellular functions of galectins.
Figure 3: Roles of galectins in tumorigenesis.
Figure 4: Galectins and tumour metastasis.
Figure 5: Galectins and tumour-associated immune and inflammatory responses.
Figure 6: Anti-tumour immune responses and galectin-mediated escape mechanisms.

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Acknowledgements

We thank members of our laboratories for stimulating discussions and helpful suggestions, in particular D. Hsu, I. Kuwabara, J. Newman, and R.-Y. Yang (in F.-T.L.'s laboratory) and M. A. Toscano, J. M. Ilarregui, N. Rubinstein, and G. A. Bianco (in G.A.R.'s laboratory). We apologize to the authors of many relevant studies not cited because of space limitations. Work in authors' laboratories was supported by grants from the National Institutes of Health to F.-T.L. and by grants from Sales Foundation, Antorchas Foundation, Ministry of Health (Becas 'Carrillo-O˜ativia'), Wellcome Trust, and University of Buenos Aires to G.A.R. G.A.R. is a member of CONICET.

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Authors and Affiliations

  1. Department of Dermatology, School of Medicine, University of California, Davis, Sacramento, California, USA

    Fu-Tong Liu

  2. Division of Immunogenetics, Hospital de Cl'nicas, School of Medicine, University of Buenos Aires, Buenos Aires, Argentina

    Gabriel A. Rabinovich

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  1. Fu-Tong Liu
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  2. Gabriel A. Rabinovich
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Corresponding authors

Correspondence to Fu-Tong Liu or Gabriel A. Rabinovich.

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DATABASES

Entrez Protein

BCL2

Galectin-1

Galectin-2

Galectin-3

Galectin-4

Galectin-7

Galectin-8

Galectin-9

Galectin-12

HRAS

KIP1

KRAS

NRAS

RAF1

Synexin

TTF1

WAF1

FURTHER INFORMATION

The Consortium for Functional Glycomics

The Japanese Consortium for Glycobiology and Glycotechnology

Glossary

MACROPHAGES

Cells of the mononuclear-phagocyte system that can phagocytose foreign particulate materials. Macrophages are present in many tissues and are important for the innate and immune reactions. They can also function as antigen-presenting cells and as effector cells in humoral and cell-mediated adaptive immunity. They have a vital role in host defense.

SCID MICE

Mice that are homozygous for the severe combined immunodeficiency (SCID) mutation have compromised B- and T-cell immunity. This lack of immunity means that they can support human tumour xenografts for preclinical studies.

DENDRITIC CELL

Specialized antigen-presenting cell whose immunogenicity leads to the induction of antigen-specific immune responses. Dendritic cells have been used in clinical trials to induce anti-tumour immune responses in cancer patients.

GRAFT-VERSUS-HOST DISEASE

In organ transplantation, mature T lymphocytes from the donor can attack various tissues in the recipient, causing a graft-versus-host (GVH) reaction and a disease state termed graft-versus-host disease.

NEUTROPHILS

The major class of white blood cells in human peripheral blood (>70%). Neutrophils are phagocytes and have an important role in engulfing and killing extracellular pathogens. They can migrate into tissues under the influence of chemotactic stimuli, where they phagocytose materials.

MONOCYTES

Circulating white blood cells that represent about 5% of total blood leukocytes. These cells can migrate into tissues to become macrophages.

PLASMA CELL

Terminally differentiated B lymphocyte. Plasma cells are the main antibody-secreting cells of the body. They are found in the medulla of the lymph nodes, in the spleen and in bone marrow.

EOSINOPHIL

White blood cell thought to be important chiefly in defense against parasite infections and in allergic inflammation. However, they can be activated by lymphocytes of the adaptive immune response and have a role in tumour immunity.

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Liu, FT., Rabinovich, G. Galectins as modulators of tumour progression. Nat Rev Cancer 5, 29–41 (2005). https://doi.org/10.1038/nrc1527

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