First Evidence for a Role of Siglec-8 in Breast Cancer.

Sialic acid-binding immunoglobulin-like lectins (Siglecs) are involved in various immune cell-mediated diseases. Their role in cancer is poorly investigated, and research focusses on Siglec-expression on immune cells interacting with tumor cells. This study evaluates the role of Siglec-8 in breast cancer (BC). Siglec-8 expression was analyzed immunohistochemically on 235 primary BC cases and was correlated with clinical and pathological parameters and outcome. Cell culture experiments were performed with various BC cell lines. Siglec-8 was expressed in 215 BC cases and expression was lowest in triple-negative BC. It correlated with estrogen receptor-status, grading and the prognostic factors galectin (Gal)-7 and tumor-associated mucin-1 (TA-MUC1). However, Gal-7 and TA-MUC1 were only prognosticators for clinical outcome in the cohort expressing high (Immunoreactivity score IRS > 3) Siglec-8 levels but not in the low-expressing cohort. Siglec-8 knockdown led to a significantly reduced Gal-7 expression in MCF7 cells. All BC cell lines expressed low Siglec-8-levels, that could be elevated in MCF7 by Peroxisome proliferator-activated receptor (PPARγ)-stimulation. This study demonstrates that Siglec-8 is expressed in BC cells and correlates with known clinical and prognostic parameters. It is probably associated with Gal-7 and TA-MUC1 and might be regulated via PPARγ. Further analyses focusing on functional associations will clarify Siglec-8's eligibility as a possible therapeutic target.

The association between oxidative stress-induced galectins and differentiation of human promyelocytic HL-60 cells.

Galectins are multifunctional ß-galactoside-binding proteins that are involved in the regulation of cellular stress responses and differentiation. The relationship between these processes is unclear and we report here that galectins display oxidative-stress specific expression patterns in neutrophil-like differentiated HL-60 cells. Three galectins (-1, -3, and -10) are upregulated in response to either menadione or DMSO exposure whereas galectins -9 and -12 exhibited a stimulus-dependent downregulation. Changes in galectin expression are oxidant dependent based on the observations that 1) oxidative stress biomarkers HMOX1 (heme oxygenase-1) and NCF1 (neutrophil cytosolic factor 1, which is also a biomarker of neutrophil differentiation) are elevated in both cases, and 2) the antioxidant N-acetyl-L-cysteine restores basal expression of galectin-3 following oxidant exposure. In addition, our results suggest that the regulation of oxidative stress-sensitive galectins involves DNA hypomethylation mechanisms. Expression of galectin-3 and galectin-12 exhibits an opposite relationship to the expression of HMOX1/NCF1, suggesting a stimulatory and inhibitory role of these galectins in neutrophil-like differentiation of HL-60 cells. We also show that the inhibition of galectins reduces the growth rate of HL-60 cells, and facilitates their neutrophil-like differentiation. Collectively, our findings indicate that the process of cellular differentiation implicates, in part, oxidative stress-sensitive galectins, which further highlights a biological significance of galectin network remodeling in cells.

Galectin-related protein: An integral member of the network of chicken galectins: 2. From expression profiling to its immunocyto- and histochemical localization and application as tool for ligand detection.

BACKGROUND: Galectin-related protein (GRP), present in vertebrates, is special within this family of adhesion/growth-regulatory proteins due to its strong positive selection and loss of canonical lectin activity. METHODS: RT-PCR and Western blotting together with flow cytofluorimetry and immunocyto- and histochemistry monitor expression and localization of chicken GRP. The promoter sequence of the GRP gene is processed computationally to detect putative sites for binding transcription factors. The labeled protein is applied as probe to detect binding sites on cells and in sections, along with glycocompounds to test inhibition of the association. RESULTS: Expression of GRP in chicken is limited to bursa of Fabricius, immunohistochemically found in B cells, also in bursal epithelium and vessels. Presence in B cells is shared with only one canonical galectin, i.e. CG-8. Binding to a chicken lymphoma line was specific and saturable, not affected by lactose but completely blocked by heparin, as also seen in sections. CONCLUSIONS: Expression monitoring initiated for GRP reveals a distinct site of localization in chicken, much more restricted than for any of its canonical galectins.

Galectins are human milk glycan receptors.

The biological recognition of human milk glycans (HMGs) is poorly understood. Because HMGs are rich in galactose we explored whether they might interact with human galectins, which bind galactose-containing glycans and are highly expressed in epithelial cells and other cell types. We screened a number of human galectins for their binding to HMGs on a shotgun glycan microarray consisting of 247 HMGs derived from human milk, as well as to a defined HMG microarray. Recombinant human galectins (hGal)-1, -3, -4, -7, -8 and -9 bound selectively to glycans, with each galectin recognizing a relatively unique binding motif; by contrast hGal-2 did not recognize HMGs, but did bind to the human blood group A Type 2 determinants on other microarrays. Unlike other galectins, hGal-7 preferentially bound to glycans expressing a terminal Type 1 (Galß1-3GlcNAc) sequence, a motif that had eluded detection on non-HMG glycan microarrays. Interactions with HMGs were confirmed in a solution setting by isothermal titration microcalorimetry and hapten inhibition experiments. These results demonstrate that galectins selectively bind to HMGs and suggest the possibility that galectin-HMG interactions may play a role in infant immunity.

Variants in the LGALS9 Gene Are Associated With Development of Liver Disease in Heavy Consumers of Alcohol.

BACKGROUND & AIMS: Alcohol consumption is a major cause of chronic liver disease and contributes to a large proportion of cirrhosis-related deaths worldwide. However, only a fraction of heavy consumers of alcohol develop advanced alcoholic liver disease (ALD), so there are likely to be other risk factors. We investigated whether polymorphisms in the gene encoding galectin-9 (LGALS9), previously shown to mediate liver injury, were associated with the development of ALD. METHODS: We isolated DNA from peripheral blood mononuclear cells (PBMCs) of 575 individuals with at-risk alcohol consumption but no other risk factors for chronic liver disease; all subjects were white Europeans who had consumed more than 80 grams ethanol per day. Of the subjects, 388 had ALD (including, 268 with cirrhosis and 74 with alcoholic hepatitis; mean age, 49 y; 72% male) and 187 had normal liver function with no biochemical or clinical evidence of liver disease (controls; mean age, 42 y; 73% male). Select LGALS9 polymorphisms were genotyped using allelic discrimination. We also genotyped and measured expression of LGALS9 messenger RNA in PBMCs from individuals who were not heavy consumers of alcohol. RESULTS: We used data from the HapMap project to identify 5 single-nucleotide polymorphisms (SNPs) that tag all the common haplotypes. When we looked for these SNPs in individuals with vs without liver disease, 4 (rs3751093, rs4239242, rs732222, and rs4794976) were associated with an increased risk of developing ALD. We found that levels of LGALS9 messenger RNA and protein expressed were associated with an allele carried by PBMCs. Multivariate analysis confirmed that rs4239242 and rs4794976 were associated with an increased risk of ALD. CONCLUSIONS: In a genetic analysis of heavy consumers of alcohol, we associated 2 SNPS in LGALS9 with the development of ALD. Although larger studies are required, this information could be used to determine the risk of individuals developing ALD or to develop therapeutic agents.

Pattern of galectins expression in actinic cheilitis with different risks of malignant transformation.

BACKGROUND: Actinic cheilitis (AC) is a chronic inflammatory lesion that in some situations can turn into squamous cell carcinoma of the lip. The molecular mechanisms involved in this process are not yet completely understood. This study aimed to investigate the expression pattern of galectins in actinic cheilitis according to the histopathological grading. METHODS: Immunoexpression of galectin-1, galectin-3, galectin-7, and galectin-9 was semiquantitatively analyzed in 65 cases of actinic cheilitis graded as low risk (n = 40) or high risk (n = 25) of malignant transformation. Association between the location of the galectins in the cellular compartments and histopathological grading was analyzed. RESULTS: Galectin-1 was mainly observed in the cell cytoplasm, and was elevated (score 3) in 60% of cases, regardless of the histopathological grade (P > 0.05). Galectin-3 expression was higher in high-risk group than in the low-risk group (P < 0.05), with a predominant expression in the cytoplasm and nucleus of low-risk (67.5%), and only in the cytoplasm of high-risk cases (60%) (P < 0.05). Galectin-7 expression did not show significant differences between low-risk and high-risk groups (P > 0.05). With respect to galectin-9, 89.2% of cases were positive, showing decrease in median of scores as there was an increase in histological grade (P < 0.001), with predominant expression in the nucleus and cytoplasm. CONCLUSIONS: This study is the first indication of galectins involvement in the pathogenesis and morphologic progression of actinic cheilitis, particularly galectin-3 and galectin-9.

Galectin-9 and IL-21 mediate cross-regulation between Th17 and Treg cells during acute hepatitis C.

Loss of CD4 T cell help correlates with virus persistence during acute hepatitis C virus (HCV) infection, but the underlying mechanism(s) remain unknown. We developed a combined proliferation/intracellular cytokine staining assay to monitor expansion of HCV-specific CD4 T cells and helper cytokines expression patterns during acute infections with different outcomes. We demonstrate that acute resolving HCV is characterized by strong Th1/Th17 responses with specific expansion of IL-21-producing CD4 T cells and increased IL-21 levels in plasma. In contrast, viral persistence was associated with lower frequencies of IL-21-producing CD4 T cells, reduced proliferation and increased expression of the inhibitory receptors T cell immunoglobulin and mucin-domain-containing-molecule-3 (Tim-3), programmed death 1 (PD-1) and cytotoxic T-lymphocyte antigen 4 (CTLA-4) on HCV-specific CD8 T cells. Progression to persistent infection was accompanied by increased plasma levels of the Tim-3 ligand Galectin-9 (Gal-9) and expansion of Gal-9 expressing regulatory T cells (Tregs). In vitro supplementation of Tim-3(high) HCV-specific CD8 T cells with IL-21 enhanced their proliferation and prevented Gal-9 induced apoptosis. siRNA-mediated knockdown of Gal-9 in Treg cells rescued IL-21 production by HCV-specific CD4 T cells. We propose that failure of CD4 T cell help during acute HCV is partially due to an imbalance between Th17 and Treg cells whereby exhaustion of both CD4 and CD8 T cells through the Tim-3/Gal-9 pathway may be limited by IL-21 producing Th17 cells or enhanced by Gal-9 producing Tregs.

The endocannabinoid anandamide affects the synthesis of human syncytiotrophoblast-related proteins.

The human syncytiotrophoblast (hST) has a major role in the production of important placental hormones. Several molecules regulate hST endocrine function but the role of endocannabinoids in this process is still unknown. Here, we report that the endocannabinoid anandamide (AEA) decreased cAMP levels, impaired human chorionic gonadotropin secretion, placental alkaline phosphatase activity and decreased aromatase mRNA levels and protein expression, through cannabinoid (CB) receptor activation. AEA also downregulated leptin and placental protein 13 transcription, though via a CB receptor-independent mechanism. All this evidence suggests AEA is a novel modulator of hormone synthesis by the syncytiotrophoblast, supporting the importance of the endocannabinoid signalling in placental function.

Galectin-9 predicts postoperative recurrence and survival of patients with clear-cell renal cell carcinoma.

Galectin-9 (Gal-9), a member of animal lectin family with evolutionary conserved carbohydrate recognition domains, has been reported to exert a large variety of functional roles in tumorigenesis due to its ß-galactoside-binding affinity. The aim of this study is to evaluate the expression and prognostic significance of Gal-9 in patients with clear-cell renal cell carcinoma (ccRCC). The expression of Gal-9 was assessed by immunohistochemistry in 196 patients with ccRCC who underwent nephrectomy. In the cohort, 48 patients died and 61 patients suffered recurrence. Kaplan-Meier method with log-rank test was applied to compare survival curves. The authors employed univariate and multivariate Cox regression models to evaluate the prognostic value of Gal-9 expression in overall survival (OS) and recurrence-free survival (RFS). In patients with ccRCC, Gal-9 expression, which was positively associated with tumor size (P = 0.014), Fuhrman grade (P = 0.010), and necrosis (P = 0.025), was determined to be an independent prognostic indicator for OS (hazard ratio [HR] 2.394; P = 0.005) and RFS (HR 2.096; P = 0.006). High expression of Gal-9 was associated with poor survival (P = 0.001) and early recurrence (P = 0.006). Furthermore, Gal-9 expression could significantly stratify the patients in early (grades I + II) tumor, node, and metastasis (TNM) stage (OS: P = 0.005; RFS: P = 0.041) and low (grades 1 + 2) Fuhrman grade (OS: P = 0.004; RFS: P = 0.006). The prognostic accuracy of TNM, SSIGN, and UISS prognostic models was improved when Gal-9 expression was added. Gal-9 expression is a potential independent prognostic factor for OS and RFS in patients with ccRCC.

Evaluation of matricellular proteins in systemic and local immune response to Mycobacterium tuberculosis infection.

Matricellular proteins such as osteopontin (OPN), galectin-9 (Gal-9), and tenascin-C (TN-C) are expressed not only under normal physiological conditions, but also during infection, inflammation and tumorigenesis. Plasma concentrations of matricellular proteins were studied to determine their diagnostic value as potential markers of tuberculosis (TB) activity. It was found that concentrations of OPN and TN-C were higher in patients with active TB than in healthy controls and individuals with latent infection. Moreover, LTBI patients had higher concentrations of OPN than did healthy controls. Gal-9 concentrations did not differ significantly between groups. Concentrations of matricellular proteins were higher in pleural fluid than in the plasma of patients with TB. Expression of matricellular proteins was also investigated in TB granulomas and other granulomatous diseases. Positive OPN and Gal-9 staining was observed in TB and sarcoidosis granulomas, but not in Crohn disease granulomas. The fibrotic ring around granulomas stained positive for TN-C in TB and sarcoidosis, but not in Crohn disease. Of the three matricellular proteins studied, OPN and TN-C may serve as reliable plasma markers for monitoring TB activity, whereas Gal-9 seems to be expressed more at the site of infection than in the systemic circulation.

Identification of lineage relationships and novel markers of blood and skin human dendritic cells.

The lineage relationships and fate of human dendritic cells (DCs) have significance for a number of diseases including HIV where both blood and tissue DCs may be infected. We used gene expression profiling of human monocyte and DC subpopulations sorted directly from blood and skin to define the lineage relationships. We also compared these with monocyte-derived DCs (MDDCs) and MUTZ3 Langerhans cells (LCs) to investigate their relevance as model skin DCs. Hierarchical clustering analysis showed that myeloid DCs clustered according to anatomical origin rather than putative lineage. Plasmacytoid DCs formed the most discrete cluster, but ex vivo myeloid cells formed separate clusters of cells both in blood and in skin. Separate and specific DC populations could be determined within skin, and the proportion of CD14(+) dermal DCs (DDCs) was reduced and CD1a(+) DDCs increased during culture, suggesting conversion to CD1a(+)-expressing cells in situ. This is consistent with origin of the CD1a(+) DDCs from a local precursor rather than directly from circulating blood DCs or monocyte precursors. Consistent with their use as model skin DCs, the in vitro-derived MDDC and MUTZ3 LC populations grouped within the skin DC cluster. MDDCs clustered most closely to CD14(+) DDCs; furthermore, common unique patterns of C-type lectin receptor expression were identified between these two cell types. MUTZ3 LCs, however, did not cluster closely with ex vivo-derived LCs. We identified differential expression of novel genes in monocyte and DC subsets including genes related to DC surface receptors (including C-type lectin receptors, TLRs, and galectins).

Lectin engineering, a molecular evolutionary approach to expanding the lectin utilities.

In the post genomic era, glycomics--the systematic study of all glycan structures of a given cell or organism--has emerged as an indispensable technology in various fields of biology and medicine. Lectins are regarded as "decipherers of glycans", being useful reagents for their structural analysis, and have been widely used in glycomic studies. However, the inconsistent activity and availability associated with the plant-derived lectins that comprise most of the commercially available lectins, and the limit in the range of glycan structures covered, have necessitated the development of innovative tools via engineering of lectins on existing scaffolds. This review will summarize the current state of the art of lectin engineering and highlight recent technological advances in this field. The key issues associated with the strategy of lectin engineering including selection of template lectin, construction of a mutagenesis library, and high-throughput screening methods are discussed.

Galectins and neovascularization in central nervous system tumors.

Despite advances in diagnosis and treatment, the overall outcomes for patients with brain tumors remain unpredictable. New prognostic markers are still needed to identify high-risk patients for whom the standard treatment has poor outcomes and would thus be well suited for more aggressive therapies. Neovascularization has long been implicated as a salient feature of glioma progression. In fact, high-grade gliomas are among the most vascular of all solid tumors, and vascular proliferation is a pathological hallmark of glioblastomas. Galectins are known to play important roles in cancer biology, including cancer cell migration, tumor immune escape or tumor angiogenesis. Moreover, galectins were reported to be involved in glioma progression. Given the key role of angiogenesis in brain tumors, the expression of galectins in tumor-associated endothelial cells (EC) and the implication of galectins in angiogenesis, the present review will focus on the expression of galectins in ECs of normal brain and brain tumors.

Lactose inhibits regulatory T-cell-mediated suppression of effector T-cell interferon-γ and IL-17 production.

Our interest in lactose as an immunomodulatory molecule results from studies showing that lactose binds to galectin-9, which has been shown to have various regulatory functions in the immune system including regulation of T-cell responses. Impaired regulation of T helper (Th)1 and Th17 type immune responses and dysfunction of regulatory T cells (Treg) have been implicated in many human immune-mediated diseases. In the present study, we investigated the effects of lactose on immune regulation using co-cultures of human peripheral blood mononuclear cell (PBMC)-derived Treg and effector T cells (Teff) obtained from twenty healthy adults. Treg, i.e. CD4+CD25+CD127-, were isolated from PBMC by immunomagnetic separation. The fraction of CD4+CD127- cells that was depleted of CD25+ cells was used as Teff. Treg and Teff at a ratio 1:5 were activated and the effects of lactose on the secretion of interferon-γ (IFN-γ) and IL-17 were analysed using ELISA for protein and quantitative RT-PCR for mRNA. Treg down-regulated the secretion of both IFN-γ (8.8-3.9 ng/ml, n 20, P= 0.003) and IL-17 (0.83-0.64 ng/ml, n 15, P= 0.04) in co-cultures, while in the presence of lactose the levels of secreted IFN-γ and IL-17 remained high and no down-regulation was observed (16.4 v. 3.99 ng/ml, n 20, P< 0.0001, and 0.74 v. 0.64 ng/ml, n 15, P= 0.005, respectively). We showed that lactose inhibits human Treg-mediated suppression of Th1 and Th17 immune responses in vitro.

Ablation of a galectin preferentially expressed in adipocytes increases lipolysis, reduces adiposity, and improves insulin sensitivity in mice.

The breakdown of triglycerides, or lipolysis, is a tightly controlled process that regulates fat mobilization in accord with an animal's energy needs. It is well established that lipolysis is stimulated by hormones that signal energy demand and is suppressed by the antilipolytic hormone insulin. However, much still remains to be learned about regulation of lipolysis by intracellular signaling pathways in adipocytes. Here we show that galectin-12, a member of a ß-galactoside-binding lectin family preferentially expressed by adipocytes, functions as an intrinsic negative regulator of lipolysis. Galectin-12 is primarily localized on lipid droplets and regulates lipolytic protein kinase A signaling by acting upstream of phosphodiesterase activity to control cAMP levels. Ablation of galectin-12 in mice results in increased adipocyte mitochondrial respiration, reduced adiposity, and ameliorated insulin resistance/glucose intolerance. This study identifies unique properties of this intracellular galectin that is localized to an organelle and performs a critical function in lipid metabolism. These findings add to the significant functions exhibited by intracellular galectins, and have important therapeutic implications for human metabolic disorders.

Up-regulated expression of Tim-3/Gal-9 at maternal-fetal interface in pregnant woman with recurrent spontaneous abortion.

The relationship between T cell immunoglobulin domain and mucin domain protein 3 (Tim-3)/Galectin (Gal)-9 pathway and recurrent spontaneous abortion (RSA) was studied. Thirty-one pregnant women with RSA and 27 normal early gravidas were investigated to detect the levels of Tim-3 and Gal-9 in villi and deciduas by Western blotting. Meanwhile, the concentration of interleukin (IL)-4 and IL-12 in peripheral blood plasma was determined by ELISA in 25 healthy fertile non-pregnant controls, the normal early gravidas and pregnant women with RSA mentioned above, respectively. It was found that the relative expression levels of Tim-3 and Gal-9 in villi and deciduas were significantly increased in pregnant women with RSA as compared with those in the normal early gravidas. The concentration of IL-4 in peripheral blood plasma of pregnant women with RSA was lower than that of the normal early gravidas (P<0.05) and healthy fertile non-pregnant controls (P<0.05), but that of IL-2 in pregnant women with RSA was significantly higher than that of the normal early gravidas (P<0.05) and healthy fertile non-pregnant controls (P<0.05). It was suggested that the overexpression of Tim-3/Gal-9 pathway may be related to the pathogenesis of RSA.

Optimization of the inter-domain structure of galectin-9 for recombinant production.

We previously developed a stable form of galectin-9, an immunomodulatory animal lectin with a truncated linker peptide (G9Null), to overcome the protease sensitivity of wild-type galectin-9. G9Null is highly resistant to proteolysis, while the modification marginally improved the low solubility of the wild-type protein. To increase its solubility, we further modified the remaining linker region of G9Null. A 10-amino acid deletion with a single amino acid substitution resulted in an ∼400% increase in solubility and yield without an adverse effect on its biological activity. This mutant protein might be useful for large-scale recombinant production needed for evaluation of the therapeutic potential of galectin-9.

Galectin-7 levels predict radiation response in squamous cell carcinoma of the cervix.

OBJECTIVE: We previously found that galectin-7 was upregulated in patients with cervical cancer who remained recurrence-free after chemoradiation. We hypothesized that pretreatment levels of galectin-7 predict radiation response in patients with squamous cell carcinoma (SCC) of the cervix. METHODS: Galectin-7 expression was assessed by immunohistochemical staining of a tissue microarray of paraffin-embedded specimens from 161 patients with cervical SCC treated with definitive radiation therapy in 1980-1999. Galectin-7 expression was scored as absent or present. Distant metastasis-free survival (DMFS), disease-specific survival (DSS), and overall survival (OS) were computed using the Kaplan-Meier method and log-rank tests. RESULTS: The median age at diagnosis was 45 years (range 21-85) and median follow-up interval was 71 months (range 0-285). Of the 161 patients, 105 (65%) had FIGO stage IB disease, 18 (11%) stage IIA, and 38 (24%) stage IIB. Median tumor diameter was 5.5 cm (range 3.5-8). Seven patients (4%) received concurrent chemotherapy; 139 patients (86%) had galectin-7-positive tumors and 22 (14%) galectin-7-negative tumors. Five-year DMFS rates for patients with galectin-7-positive versus -negative tumors were 73% and 55% (p=0.05); DSS, 65% and 36% (p=0.004); and OS, 64% and 36% (p=0.005). In multivariate analysis adjusting for age, stage, and tumor diameter, galectin-7 expression remained a significant predictor of DMFS (hazard ratio [HR]=0.43, p=0.03), DSS (HR=0.34, p=0.001), and OS (HR=0.34, p=0.001). CONCLUSIONS: Elevated galectin-7 expression is associated with improved outcomes after radiation therapy for cervical cancer. Further studies are required to validate these findings and clarify the role of galectin-7 in disease progression and radiation response.

Dysregulation of TIM-3-galectin-9 pathway in the cystic fibrosis airways.

The T-cell Ig and mucin domain-containing molecules (TIMs) have emerged as promising therapeutic targets to correct abnormal immune function in several autoimmune and chronic inflammatory conditions. It has been reported that proinflammatory cytokine dysregulation and neutrophil-dominated inflammation are the main causes of morbidity in cystic fibrosis (CF). However, the role of TIM receptors in CF has not been investigated. In this study, we demonstrated that TIM-3 is constitutively overexpressed in the human CF airway, suggesting a link between CF transmembrane conductance regulator (CFTR) function and TIM-3 expression. Blockade of CFTR function with the CFTR inhibitor-172 induced an upregulation of TIM-3 and its ligand galectin-9 in normal bronchial epithelial cells. We also established that TIM-3 serves as a functional receptor in bronchial epithelial cells, and physiologically relevant concentrations of galectin-9 induced TIM-3 phosphorylation, resulting in increased IL-8 production. In addition, we have demonstrated that both TIM-3 and galectin-9 undergo rapid proteolytic degradation in the CF lung, primarily because of neutrophil elastase and proteinase-3 activity. Our results suggest a novel intrinsic defect that may contribute to the neutrophil-dominated immune response in the CF airways.

The mRNA level of the galectin-10 of Angiostrongylus cantonensis induced by reactive oxygen stress.

Galectin plays an important role in host-parasite interactions. In this study, we identified a novel gene encoding galectin-10 (AcGal-10) from the cDNA library of Angiostrongylus cantonensis and characterized its biological role in the parasite. Sequence and phylogeny analysis showed that AcGal-10 is related to other galectin family members with the conserved loci (H(84)-D(86)-R(88)-V(96)-N(98)-W(105)-E(108)-R(110)). The mRNA level of AcGal-10 was expressed in reactive oxygen stress radicals. We have identified two proteins of A. cantonensis galectin-10 gene, one of which was reported (AcGAL10-W) and the others is AcGAL-10-M. In addition, recombinant AcGal-10 (rAcGal-10) was constructed into the pGEX-4T-1 plasmid, purified, and finally confirmed by SDS-PAGE and LC-MS. Hemagglutination assay showed that the minimum concentration of rAcGAL10-W and rAcGAL10-M required for the hemagglutination of BALB/c mice erythrocyte was 25 µg/mL, and the carbohydrate-binding ability showed no difference between rAcGAL10-W and rAcGAL10-M. The mRNA levels of AcGal-10 were indeed expressed higher after stimulation with H(2)O(2) and recombinant A. cantonensis galectin-10. A mutation of AcGal-10 was also found, but there was no significant difference compared with the wild type. Furthermore, we also confirmed that recombinant AcGal-10 plays a role in the activation of the microglia. In conclusion, the report here showed that AcGal-10 may be an important molecule related to infection of A. cantonensis.