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Varki A, Cummings RD, Esko JD, et al., editors. Essentials of Glycobiology. 2nd edition. Cold Spring Harbor (NY): Cold Spring Harbor Laboratory Press; 2009.

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Essentials of Glycobiology. 2nd edition.

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Chapter 33Galectins

and .

Galectins typically bind β-galactose-containing glycoconjugates and share primary structural homology in their carbohydrate-recognition domains (CRDs). Previously termed S-type lectins, galectins represent a group of proteins that are the most widely expressed class of lectins in all organisms. This chapter describes the diversity of the galectin family and presents an overview of what is known about their biosynthesis, secretion, and biological activities.


Following the discovery of agglutinins in plants and lectins (discoidin I) in Dictyostelium discoideum in the early 1970s, many investigators began to search for lectins in animal tissues. As noted in Chapter 26, the first reported lectin in animal cells was the hepatic asialo-glycoprotein receptor, a C-type lectin. The next lectin found in animals was the protein now recognized as the first galectin. It was originally described in 1975 during studies on the possible presence of lectins in the electric organs of the electric eel. The protein, termed electrolectin, had hemagglutinating activity with trypsinized rabbit erythrocytes that was inhibitable by β-galactosides and could be isolated by affinity chromatography on β-galactoside supports. Notably, this protein required the inclusion of β-mercaptoethanol in isolation buffers to maintain its activity, suggesting the presence of one or more free cysteine residues. The galectins were originally referred to as S-type lectins to denote their sulfhydryl dependency, the presence of cysteine residues, their solubility, and their shared primary sequence, in much the same way that the designation C-type denotes Ca++ dependency and shared primary structure for that class of lectins. However, electrolectin, unlike most galectins, does not contain cysteine residues, but its key tryptophan residue in the binding site of its CRD can be oxidized, causing loss of activity. Electrolectin is approximately 15 kD in size and occurs as a noncovalently linked homodimer.

The first galectins found in vertebrates were isolated in 1976 from chick muscle and from extracts of calf heart and lung. Lactose was required to isolate the mammalian lectin, now termed galectin-1, from macromolecular glycoconjugates in calf heart/lung extracts. Galectin-1 was purified by affinity chromatography on asialofetuin-Sepharose and it also required reducing conditions to maintain activity. The calf heart/lung galectin-1 is approximately 15 kD in size and occurs as a noncovalent dimer. In the early 1980s, a 35-kD carbohydrate-binding protein (CBP35; now known as galectin-3) that also bound to β-galactosides was identified from mouse fibroblasts. The same protein had been studied by other groups and was known as IgE-binding protein (ɛBP), L-29, and L-31. All of these proteins demonstrated hemagglutinin activity, but the choice of erythrocytes was crucial. Trypsinized rabbit erythrocytes, which display more terminal galactose residues than human erythrocytes, are readily agglutinated by most galectins, whereas human erythrocytes require treatment with neuraminidase to enhance their agglutinability. The nomenclature for galectins was systematized in 1994. The first galectin found (variously termed electrolectin, β-galactoside-binding lectin, galaptin, L-14, etc., depending on its source) was renamed galectin-1. Its nearest homolog was termed galectin-2. CBP35, ɛBP, L-29, and L-31 were termed galectin-3, and other members of this family were numbered consecutively by order of discovery.


The canonical CRD of galectins has approximately 130 amino acids, although only a small number of residues within the CRD directly contact glycan ligands. A comparison of the sequences of approximately 130 galectins from many different sources reveals that eight residues, which have been shown to be involved in carbohydrate binding by X-ray crystallographic analyses, are invariant. In addition, another dozen residues appear to be highly conserved. Part of the highly conserved sequence motif used to identify galectins is shown in Figure 33.1, along with a comparison of several human galectins. On the basis of sequence homologies, two general subgroups of galectins can be distinguished: the galectin-1 subgroup, which includes galectin-1 and galectin-2, and the galectin-3 subgroup, which includes all others. In comparison to human galectin-1, the mushroom galectin from Coprinus cinereus is overall about 20% identical and the 14-kD and 16-kD galectins in chickens are both about 60% identical.

FIGURE 33.1. Different types of galectins in humans.


Different types of galectins in humans. (a) Human galectins have been classified into three groups according to their structure: prototypical, chimeric, and tandem repeat. The carbohydrate-recognition domain (CRD) of most galectins is approximately 130 (more...)

A large number of galectins have now been identified in animals based on the conserved galectin CRD, and although most of them recognize simple β-galactosides, the binding affinity for such structures is relatively weak. A list of the human galectins known to bind β-galactosides is shown in Figure 33.1. A total of 15 galectins have now been found in mammals, but only 12 galectin genes are found in humans, including two for galectin-9. These have been classified into three major groups:

  1. The prototypical galectins, which contain a single CRD that may associate to form homodimers.
  2. The chimeric galectins, of which galectin-3 is the only known species found in vertebrates. Galectin-3 is characterized by having a single CRD and a large amino-terminal domain, which is rich in proline, glycine, and tyrosine residues, similar to those found in some other proteins (such as synexin and synaptophysin), where it may contribute to self-aggregation. In addition, the amino-terminal domain is sensitive to metalloproteinases, such as MMP-2 and MMP-9. Chimeric galectins are more common in invertebrates.
  3. The tandem-repeat galectins, in which at least two CRDs occur within a single polypeptide. They are bridged or linked by a small peptide domain. These link domains can range from 5 to more than 50 amino acids in length.

In addition, many of the galectin transcripts may be differentially spliced to generate many different isoforms. For example, at least seven different mRNAs have been identified for human galectin-8, some encoding a tandem-repeat form and others a prototypical form. These isoforms of galectin-8 may be differentially expressed in different tissues. Three isoforms of galectin-9 differing in the length of the linker domains have been identified. Similarly, different splice forms of pig galectin-4 generate long and short forms. Galectin-5 (prototypical) and galectin-6 (tandem-repeat) are found in rodents, but not humans, and galectin-11 (ovagal11; prototypical) has been reported in sheep. Confusingly, the GRIFIN protein (prototypical), which in mammals may not bind to carbohydrates, has also been termed galectin-11 (but see below).

There are also a number of galectin-related proteins that have homology with galectins, but they may not bind carbohydrates, or at least not bind to typical β-galactosides. For example, galectin-10 appears to bind better to β-mannosides than to β-galactosides. Galectin-10 is primarily expressed in eosinophil granules and occurs there in a crystalline form, known as the Charcot–Leyden crystal protein. Several proteins in vertebrates related to galectin-10 do not appear to bind sugars (GRIFIN, PP-13, PPL-13, and the sheep protein ovgal11). These proteins may be thought of as a subfamily of galectin-10. It is also possible that the correct glycan ligands have not yet been identified. Interestingly, the GRIFIN homolog in zebrafish Danio rerio, DrGRIFIN, is a functional β-galactoside-binding protein and has a more galectin-like sequence. Like mammalian GRIFIN, DrGRIFIN is also highly expressed in the eye lens. Galectin-10 family members may be generally thought of as crystalline proteins. Another galectin-related protein (GRP) is HSPC159, which is expressed in human hematopoietic stem cell precursors, but it lacks a critical tryptophan residue that is highly conserved in all other galectins; thus, it may be unable to bind β-galactosides.

Galectins are found in virtually all organisms. Birds express 14-kD and 16-kD galectins that are related to galectin-1 and other galectins that are homologs of galectin-3 and -8. Galectins have also been found in the skin (16 kD) and oocytes (15 kD) of the amphibians Xenopus laevis and Bufo arenarum, respectively, and homologs of galectin-1, -3, -4, -8, and -9, and HSPC159 have been found in X. laevis. Fish galectins have also been found and partly characterized, including homologs of galectin-1, -3, -4, and -9, and HSPC159. Zebrafish has three genes that have homology with galectin-1, along with genes for homologs of galectin-4 and galectin-9 and HSPC159. Galectins are also expressed in Drosophila melanogaster (six candidate genes) and Caenorhabditis elegans (26 candidate genes). At least 14 of these candidate galectin genes in C. elegans have been shown to encode proteins and are found as expressed sequence tags (ESTs). Galectins have also been found in sponges (Geodia cydonium), and there are galectin-like sequences predicted from the plant genome (Arabidopsis thaliana). Interestingly, some of the predicted galectin genes in C. elegans and plants encode proteins that might contain a galectin domain in tandem with a glycosyltransferase domain, and some of these proteins may have standard signal sequences. Galectin-like proteins are even expressed in some viruses that infect pigs and fish, including porcine adenovirus and lymphocystis disease virus.


The interactions of galectins with glycans are complex and several factors contribute to high-affinity binding, including the natural multivalency and oligomeric state of the galectins, the multivalency of their natural glycoconjugate ligands, and the mode of presentation of the glycans. In simple terms, most members of the galectin family tested so far bind simple β-galactosides, such as disaccharides or trisaccharides, but the affinity is relatively weak (i.e., in the high micromolar to low millimolar range). In contrast, galectin binding to natural glycoconjugate ligands expressed on cell surfaces or in the extracellular matrix is usually of much higher affinity (i.e., in the micromolar or submicromolar range). Each galectin CRD recognizes different types of glycan ligands and shows highest affinity binding to different structures. For example, galectin-3 binds tightly to glycans with repeating [-3Galβ1-4GlcNAcβ1-]n or poly-N-acetyllactosamine sequences containing three to four repeating units, regardless of the presence of a terminal β-galactose residue. In contrast, human galectin-1 also binds well to long poly-N-acetyllactosamine chains, but it requires a terminal β-galactose residue. Although galectin-3 binds weakly to single N-acetyllactosamine units, its binding to these units is enhanced if the penultimate galactose residues are substituted with Galβ1-3, GalNAcα1-3, or Fucα1-2 residues. In contrast, such substitutions dramatically decrease binding by galectin-1. Galectin-8 has two CRDs within its single polypeptide, and the amino- and carboxy-terminal CRDs bind different glycans. For example, the amino-terminal CRD of human galectin-8 binds α2-3-sialylated glycans with high affinity (Kd of ~50 nM), whereas the carboxy-terminal CRD shows lower-affinity binding, primarily to the blood group A determinant GalNAcα1-3(Fucα1-2)Gal- on either a LacNAc or Galβ1-3GlcNAc core, and does not bind sialylated glycans.

Cocrystallization of galectins with simple β-galactose-containing disaccharides has revealed that many galectins bind to the C-4 and C-6 hydroxyls of galactose and the C-3 hydroxyl of N-acetylglucosamine. The binding sites of galectins may be viewed as containing several subsites: one for galactose, another for N-acetylglucosamine, and still other sub-sites that may be filled by other sugars and the aglycone moiety, such as a peptide or lipid.

Galectins appear to bind selectively to some cell-surface and extracellular matrix ligands. However, the precise physiological roles of these interactions with each galectin are not well understood. Potential ligands for galectin-1 and galectin-3 include basement membrane proteins (such as laminin and fibronectin), membrane receptors (such as integrins α7β1 and α1β1, CD43, CD7, and CD45), lysosome-associated membrane proteins (LAMP-1 and LAMP-2), vitronectin, and fibronectin. Galectin-1 interactions with T-cell glycoproteins (such as CD43 and CD45) depend on appropriate glycosylation by specific glycosyltransferases (such as the core-2 β1-6 N-acetylglucosaminyltransferase that forms core-2 O-glycans and the β1-6 N-acetylglucosaminyltransferase V that forms branched N-glycans). However, the precise glycan structures on these macromolecules recognized by galectins are not well defined.

Galectin-8 displays high-affinity binding in the extracellular matrix to integrins and to a variant of CD44, and its binding to integrins (α3β1 and α6β1) modulates their adhesive and signaling properties. Depending on its expression level, galectin-8 may diminish integrin-dependent adhesion or enhance it. Galectin-8 binding to CD44v is high affinity (Kd of 6 nM). Galectin-9 binds to TIM-3, which is a membrane-bound T-cell immunoglobulin-like protein with O-glycans. TIM-3/galectin-9 appears to contribute to T-helper 1 (Th1) cell immunity and tolerance induction.


All members of the galectin family lack a classical signal sequence and membrane-anchoring domains and appear to be synthesized on free polysomes in the cytoplasm and accumulate there prior to secretion. Galectins are probably unique among all types of animal lectins in that they can be found in the nucleus, cytoplasm, outer plasma membrane, and extracellular matrix. One rather common modification of galectins in animal cells is blockage of the amino terminus. Galectin-3 has been shown to also have a serine residue in its amino-terminal region that can be phosphorylated. Newly synthesized galectins isolated directly from the cytoplasm of cells are functional in binding β-galactosides, indicating that they are synthesized and potentially functional in that compartment. Interestingly, there is little evidence for the presence of galectin glycan ligands in the cytoplasm, indicating that they may have other functions there.

As discussed below, however, there is compelling evidence for galectins having noncarbohydrate-binding partners in the cytoplasm. The complexity of galectin biosynthesis, secretion, and oligomerization is illustrated schematically for galectin-1 in Figure 33.2. Curiously, the export of galectins from cells does not involve direct movement through the secretory apparatus. The mysterious process, termed nonclassical export, by which these proteins are exported has been explored in several ways, but the basic mechanism is still unknown. Several other relatively small-sized growth factors and cytokines (e.g., fibroblast growth factors FGF-1 and FGF-2 and interleukin IL-1β) are also secreted by a nonclassical pathway, but whether their secretory pathway converges with that of galectins is not known.

FIGURE 33.2. Possible biosynthetic routes for galectins in animal cells.


Possible biosynthetic routes for galectins in animal cells. The mRNA for the protein is translated on free polysomes in the cytoplasm, and the newly synthesized protein is capable of binding carbohydrate ligands or interacting with other proteins within (more...)

In exploring a possible mechanism for export, recombinant galectin-1 expressed in yeast was found to be exported by a transmembrane protein, but so far this transporter appears to be limited to yeast. Whether different transporters occur in animal cells is unknown. It is also possible that export involves membranous structures. For example, galectin-1 appears to exit from myoblasts via evaginations of the plasma membrane, which pinch off to form lectin-enriched vesicles. Similarly, galectin-3 assembles into patches that eventually appear to underlie the plasma membrane as a prelude to deposition in the extracellular space, possibly through vesicular extravasation. Removal of the unique amino-terminal 11 amino acids in galectin-3 prevents its export. Although the mechanism of export is unclear, several galectins, including galectin-1, rapidly lose activity in a nonreducing environment at 37°C, as exists outside cells. In contrast, other galectins, such as galectin-3 and galectin-4, are highly stable in such an environment. Studies on the biosynthesis of galectin-1 found that the newly exported protein is extremely unstable in the absence of glycan ligands, but when high-affinity ligands are available, the protein is stable. Thus, the regulated secretion and availability of glycan ligands may also regulate activity and stability of galectins.


The crystal structures of several galectins have now been reported, including bovine galectin-1 (complexed with either N-acetyllactosamine or diantennary N-glycans), human galectin-2, -3, and -7, and individual domains of galectin-9 (complexed with monosaccharides or small glycans such as lactose). All of the structures show that the CRD of galectin subunits is composed of five- and six-stranded antiparallel β-sheets arranged in a β-sandwich or jelly-roll configuration that completely lacks an α-helix (Figure 33.3). In the dimeric proteins, such as galectin-1, -2, and -7, the subunits are related by a twofold rotational axis perpendicular to the plane of the β-sheets. The glycan-binding sites in the CRD are located at opposite ends of the dimer, although the orientation of the subunits in the galectin-7 dimer is different from that of the other canonical galectin dimers. The compactly arranged structure of the CRD partly explains the protease resistance of the galectin CRD and the high degree of conservation and requirement for 130 amino acids in the CRD. Such folded structures are similar in some ways to the folds in many plant L-type lectins from legumes and those in pentraxins, although the primary sequences of galectins have no similarities to those of other classes of proteins. The complete three-dimensional structures of many other galectins, such as tandem-repeat galectins, have not been determined, because such galectins do not crystallize well, possibly because of disorder introduced by the bridging or linking peptide.

FIGURE 33.3. (a) Ribbon diagram of the crystal structure of human galectin-1, based on X-ray crystallographic analyses of the protein complexed with lactose.


(a) Ribbon diagram of the crystal structure of human galectin-1, based on X-ray crystallographic analyses of the protein complexed with lactose. The homodimer is shown with each monomer colored differently and orthogonal views are presented. The subunit (more...)

The galectin-1 CRD displays highly specific interactions with galactose and N-acetylglucosamine residues. Interactions with carbohydrates generally are through hydrogen bonding, electrostatic interactions, and van der Waals interactions through ring stacking with galactose and the highly conserved tryptophan residue (Figure 33.3). In general, the open-ended structure of the carbohydrate-binding site is predicted to allow access to extended galactose-containing glycans, such as the poly-N-acetyllactosamines and blood-group-related structures. Several known and predicted subsites on galectins near the carbohydrate-binding site could serve to enhance affinity for more extended glycans. Some of these subsites have been identified by cocrystal structural analysis with glycans and by glycan-binding studies. The crystal structure of bovine galectin-1 was derived for the protein in complex with a biantennary N-glycan containing two terminal β-galactose residues. In this extended crystal structure, the N-glycan is bridged between two galectin dimers, thus effectively creating a crystal latticework. This type of crystal latticework may be unique among galectins in regard to vertebrate galectins and may be critical for their signaling and adhesive functions.

Some galectins rapidly lose activity (within a day) if not kept in reducing buffers, perhaps due to cross-linking and oxidation of cysteine residues or the key tryptophan residue in the CRD. The most labile lectin in this regard is vertebrate galectin-1. The presence of even weak binding ligands, such as lactose, can help stabilize vertebrate galectin-1 in the absence of reducing conditions. However, most others such as galectin-3 or galectin-4 are stable in the absence of reducing conditions or ligands. Interestingly, many of the galectins have free reduced cysteine residues, a situation that is perhaps predictable since they are synthesized in the cytoplasm, which is a highly reducing environment. Interestingly, for galectin-1 there is evidence that, upon oxidation, it can also form intramolecular disulfides, which are coincident with a loss of carbohydrate-binding activity. Curiously, this alternative oxidized galectin-1 has activity in promoting axonal regeneration in adult rat dorsal root ganglia.


Galectins are probably the most ancient class of glycan-binding proteins, and they are found in all metazoans examined, from sponges and fungi to both invertebrates and vertebrates. Galectins can contribute to cell–cell and cell–matrix interactions, and galectin signaling at the cell surface can also modulate cellular functions. In addition, intracellular galectins may interact with intracellular ligands to regulate cellular activities and may contribute to some fundamental processes such as pre-mRNA splicing (Figure 33.4). Examples of the functions and activities associated with different galectins, with emphasis on their roles in immune regulation and inflammation, are shown in Figure 33.5.

FIGURE 33.4. Functional interactions of galectins with cell-surface glycoconjugates and extracellular glycoconjugates can lead to cell adhesion and cell signaling.


Functional interactions of galectins with cell-surface glycoconjugates and extracellular glycoconjugates can lead to cell adhesion and cell signaling. Interactions of galectins with intracellular ligands may also contribute to the regulation of intracellular (more...)

FIGURE 33.5. A list of known and putative functions and biological activities of galectins toward cells in the immune system.


A list of known and putative functions and biological activities of galectins toward cells in the immune system.

Roles of Galectins in Immune Responses and Inflammation

One of the major functions of galectins is to regulate immune and inflammatory responses. Galectins are expressed by activated T and B cells, regulatory T cells, dendritic cells, mast cells, eosinophils, monocytes/macrophages, and neutrophils. In addition, galectins can promote pro- or anti-inflammatory responses, depending on the inflammatory stimulus, microenvironment, and target cells. Immune cell responses to galectins also depend on the specific glycosylation of surface glycoproteins in those cells to generate galectin ligands.

Galectin-1 function is generally associated with attenuating inflammatory responses. In contrast, galectin-3 has a proinflammatory role. For example, galectin-1 can contribute to the balance between Th1 and Th2 immune responses, which are characterized by the types of cytokines produced. Galectin-1 can induce some anti-inflammatory cytokines, such as IL-5, IL-10, and transforming growth factor-β (TGF-β) in activated T cells, and it can inhibit production of proinflammatory cytokines, such as IL-2, tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ). Th1 and Th17 differentiated cells express the types of nonsialylated glycan ligands that are essential for their binding to galectin-1 and signal responses leading to their down-regulation, whereas Th2 cells may lack these types of ligands and may have more sialylated ligands that reduce galectin-1 binding and signaling. Thus, galectin-1 knockout mice show a “hyper-Th1 and Th17 response” when challenged by antigens in vivo. Overall, it appears that the differential glycosylation of T-helper cells and their differential responses to galectins may determine the overall immune responses. Galectin-1 knockout mice also exhibit heightened sensitivity to experimental autoimmune encephalomyelitis associated with elevated levels of Th1 and Th17 lymphocytes. Interestingly, subcutaneous injections of recombinant human galectin-1 can reduce the severity of several autoimmune diseases in animal models, including experimental autoimmune encephalomyelitis, experimental autoimmune myasthenia gravis, and collagen-induced arthritis.

Galectin-1 interacts with several specific T-cell glycoproteins, including CD45, CD43, and CD7, but these interactions depend on appropriate glycosylation by specific glycosyltransferases, such as the core-2 β1-6 N-acetylglucosaminyltransferase that forms core-2 O-glycans and the β1-6 N-acetylglucosaminyltransferase V that forms branched N-glycans.

Galectin-3 is associated with activation of T cells perhaps by interacting with the poly-N-acetyllactosamine-containing N-glycans on the T-cell receptor (TCR). Expression of such N-glycans is partly regulated by branching of N-glycans through β1-6 N-acetylglucosaminyltransferase V (Mgat5). Mgat5-null mice show enhanced clustering of TCRs, indicating that branched N-glycans interacting with galectin-3 may normally restrict TCR clustering and serve as a hindrance to the development of T-cell responses. Galectin-3 can also inhibit IL-5 production in several immune cells, including human eosinophils. On the other hand, galectin-3 can activate mast cells, neutrophils, and monocytes, in terms of mediator release and production of reactive oxygen species. Lack of galectin-3 in knockout mice is associated with reduced mast cell function, reduced accumulation of asthma-associated leukocytes in airway inflammation, and reduced peritoneal inflammatory responses. Endogenous galectin-3 has also been shown to play a role in phagocytosis by macrophages and mediator release/cytokine production by mast cells by functioning intracellularly. Overall, such results suggest a complex set of functions for galectin-3 as a proinflammatory mediator and in regulating many aspects of the inflammatory response.

Roles of Galectins in Apoptosis and Induction of Cell-Surface Phosphatidylserine Exposure

Several galectins (including galectin-1, -2, -3, -7, -8, -9, and -12) have been shown to be able to induce apoptosis in some types of blood cells. For galectin-1, this activity has been studied most in human T cells, where apoptotic pathways may involve cell-surface glycoproteins including CD7, CD29, and CD43, whereas induction of apoptosis in T cells by galectin-3 involves CD71 and CD45. In some cells, apoptotic signaling may function through down-regulation of Bcl-2 and activation of caspases. The interactions of galectin-9 with Tim-3 on Th1 cells may induce their apoptosis. In addition, overexpression of intracellular galectin-3 exhibits antiapoptotic activity, whereas overexpression of galectin-7 and galectin-12 may promote apoptosis in cells. Some potential intracellular binding partners for galectins, especially galectin-3, include several proteins involved in regulating apoptosis, such as Bcl-2, Fas receptor (CD95), synexin (which is a Ca++- and phospholipid-binding protein), and Alg-2. In addition, some galectins, such as galectin-1, -2, and -4, also have the unusual ability to induce exposure of cell-surface phosphatidylserine independently of apoptotic events. In activated human neutrophils, this process induced by galectin-1 requires binding to cell-surface receptors in lipid rafts or microdomains and involves mobilization of intracellular Ca++ and signaling through Src kinase and phospholipase Cγ.

Roles of Galectins in Animal Development

Galectins play important, but rather subtle, roles in animal development. Lack of galectin-3 in knockout mice is associated with several phenotypic changes, such as fatty liver disease, reduced mast cell function, reduced liver fibrosis upon induced liver damage, and age-dependent glomerular lesions. In contrast, lack of galectin-1 in mice is associated with a different set of interesting phenotypic changes, including decreased sensitivity to noxious thermal stimuli, altered primary afferent neural anatomy, aberrant topography of olfactory axons, and reduced muscle regeneration ability after injury.

It is possible that the redundancy of galectin family members contributes to survival of these null mutants or that these particular galectins are involved only in postdevelopmental processes, such as immune regulation. Consistent with this possibility, the inflammatory response in galectin-3-null mice is dampened, and there is a decline in infiltrating neutrophils. It will be interesting to observe the phenotypes of mice with deletions of two or more galectins when they are provided with a variety of environmental, pathogenic, and antigenic challenges.

Roles of Galectins in Cancer

Many types of tumors, including melanomas, astrocytomas, and bladder and ovarian tumors overexpress various galectins, and their heightened expression usually correlates with clinical aggressiveness of the tumor and the progression to a metastatic phenotype. Three galectins that have shown importance in cancer progression and metastasis are galectin-1, -3, and -9. The immunosuppressive and apoptotic effects of galectin-1 can contribute to tumor survival, as revealed by knockdown studies, where decreased galectin-1 expression is associated with decreased tumor survival, due to increased survival of IFN-γ-producing Th1 cells and heightened T-cell-mediated tumor rejection. Recent studies using galectin-1 knockout cells have shown that expression of galectin-1 in tumor cell endothelium is essential for tumor angiogenesis. Thus, galectins are likely to play important roles in tumor progression and metastasis through indirect effects in regulating tumor immune responses and direct effects in tumor angiogenesis. Overexpression of galectin-3 correlates well with neoplastic transformation and tumor progression toward metastasis, and expression of galectin-3 may be a histological tumor marker. Some studies even suggest that blocking galectin-3 function may limit tumor metastasis.

Roles of Galectins in Innate Immunity

Although the expression of galectins in animal tissues is tightly regulated, their expression can be induced and this may be especially important in innate immune responses. For example, both galectin-1 and galectin-3 are up-regulated in gastric epithelial cells that are infected by Helicobacter pylori, and galectin-9 can be induced upon exposure of periodontal ligament cells to Porphylomonas gingivalis lipopolysaccharide. One of the galectins in Amphioxus (BbtGal-L) is up-regulated in immune organs by challenge with different pathogens. Galectins, such as galectin-3, have also been shown to bind pathogen-derived glycans directly and may function in stimulating macrophage uptake of pathogen materials for antigen presentation. Finally, galectin-3 can directly induce death of the yeast Candida albicans through binding to β1-2 oligomannosyl residues. The roles of galectins in innate defense against microorganisms have been revealed by studying genetically engineered mice deficient in specific galectins. For example, galectin-3-null mice had impaired capacities in clearing late infection of Mycobacterium tuberculosis compared to wild-type mice, suggesting involvement of galectin-3 in innate defense against Mycobacterial infection.


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Copyright © 2009, The Consortium of Glycobiology Editors, La Jolla, California.
Bookshelf ID: NBK1944PMID: 20301264


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