The role of galectin-1 in cancer progression, and synthetic multivalent systems for the study of Galectin-1

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Abstract

This review discusses the role of galectin-1 in the tumor microenvironment. First, the structure and function of galectin-1 are discussed. Galectin-1, a member of the galectin family of lectins, is a functionally dimeric galactoside-binding protein. Although galectin-1 has both intracellular and extracellular functions, the defining carbohydrate-binding role occurs extracellularly. In this review, the extracellular roles of galectin-1 in cancer processes are discussed. In particular, the importance of multivalent interactions in galectin-1 mediated cellular processes is reviewed. Multivalent interactions involving galectin-1 in cellular adhesion, mobility and invasion, tumor-induced angiogenesis, and apoptosis are presented. Although the mechanisms of action of galectin-1 in these processes are still not well understood, the overexpression of galectin-1 in cancer progression indicates that the role of galectin-1 is significant. To conclude this review, synthetic frameworks that have been used to modulate galectin-1 processes are reviewed. Small molecule oligomers of carbohydrates, carbohydrate-functionalized pseudopolyrotaxanes, cyclodextrins, calixarenes, and glycodendrimers are presented. These synthetic multivalent systems serve as important tools for studying galectin-1 mediated cancer cellular functions.

Figures

  • Figure 1. Dimeric structure of galectin-1. Galectin-1 (blue) with lactose (red) bound in the apposing carbohydrate recognition domains. Reproduced with permission from Reference [52].
  • Table 1. Galectin-1 binding partners and associated cancer processes.
  • Figure 2. Galectin-1 mediates homotypic aggregation of cancer cells through multivalent interactions with cell-surface glycoproteins on adjacent cells and through reorganization of the cell surface, which exposes adhesion molecules.
  • Figure 3. Biphasic arbitration of cell–extracellular matrix (ECM) interactions by galectin-1: (a) galectin-1 mediated cross-linking of cell-surface glycoconjugates and ECM glycoproteins promotes adhesion; and (b) competitive binding to ECM glycoproteins by galectin-1 inhibits adhesion and promotes dissemination of tumor cells.
  • Figure 4. Galectin-1 competitively binds receptors involved in cell–ECM adhesion to promote migration and invasion.
  • Figure 5. Angiogenesis. Illustration of the angiogenesis cascade that involves: (1) pericyte detachment and basal membrane degradation in response to endothelial cell activation; (2) migration of endothelial tip cells in the direction of the growth factor gradient; (3) provision of support of endothelial tip cells by the underlying stalk cells; (4) continuation of this process to form luminized vessel sprouts; (5) fusion of sprouts; and (6) formation of a functional vessel which is further stabilized by deposition of a basal membrane and attraction of pericytes for structural support [3]. Figure reproduced with permission from Reference [3]. BM, basal membrane; EC, endothelial cell.
  • Figure 6. Provision of structural support for neovasculature by galectin-1.
  • Figure 7. Galectin-1 mediated T cell apoptosis. Galectin-1 induces segregation and clustering of CD45 in distinct microdomains from CD43/CD7 complexes. Green motif, galectin-1.

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CITATION STYLE

APA

Cousin, J. M., & Cloninger, M. J. (2016, September 16). The role of galectin-1 in cancer progression, and synthetic multivalent systems for the study of Galectin-1. International Journal of Molecular Sciences. MDPI AG. https://doi.org/10.3390/ijms17091566

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