BACKGROUND AND OBJECTIVES: Existing data on the spatiotemporal expression patterns of a variety of galectins in murine atherosclerosis are limited. We investigated the expression levels of galectins, and their in vivo spatiotemporal expression patterns and statin responsiveness in the inflamed atherosclerotic plaques of apolipoprotein E (apoE)-/- mice. MATERIALS AND METHODS: Galectins expression patterns in aortic atherosclerotic plaques and serum galectin-3 levels were investigated in 26-week-old apoE-/- (n=6) and C57BL/6 mice (n=9). To investigate the spatial and temporal patterns of galectin-1 and galectin-3 in plaques, high-cholesterol diet-fed 26-week-old (n=12) and 36-week-old apoE-/- mice (n=6) were sacrificed and their aortas were examined for galectins' expression using immunoblot analysis and immunohistochemical stain. 36-week-old apoE-/- mice were treated with atorvastatin (n=3, 0.57 mg/kg/day) for the evaluation of its effect on aortic galectins' expression. RESULTS: Immunoblot analyses showed that galectin-1 and galectin-3 were the predominant galectins expressed in murine atherosclerosis. The serum galectin-3 level was significantly higher in apoE-/- mice (p<0.001). While galectin-1 was weakly expressed in both intimal plaques and the media of atherosclerotic aortas, galectin-3 was heavily and exclusively accumulated in intimal plaques. Galectin-3 distribution was colocalized with plaque macrophages' distribution (r=0.66). As the degree of plaque extent and inflammation increased, the intraplaque galectin-3 expression levels proportionally elevated (p<0.01 vs. baseline), whereas galectin-1 expression had not elevated (p=0.14 vs. baseline). Atorvastatin treatment markedly reduced intraplaque galectin-3 and macrophage signals (p<0.001 vs. baseline), whereas it failed to reduce galectin-1 expression in the aortas. CONCLUSION: Galectin-3 is the predominant gal and is colocalized with macrophages within atherosclerotic plaques. Intraplaque galectin-3 expression reflects the degree of plaque inflammation.
Animals ; Aorta ; Apolipoproteins ; Atherosclerosis ; Galectin 1 ; Galectin 3 ; Galectins ; Heptanoic Acids ; Inflammation ; Macrophages ; Mice ; Plaque, Atherosclerotic ; Pyrroles ; Atorvastatin Calcium

OBJECTIVES: There is a classical distinction based on clinical criteria between acquired and congenital cholesteatomas. To determine if these two types of lesions show different immunohistochemical features, we have studied the expression patterns of three distinctive galectins (animal lectins implied especially in cellular proliferation and apoptosis) in both types of cholesteatomas and compared it to their expression patterns in external auditory canal skin. METHODS: Our study is based on nine acquired and eight congenital cholesteatomas, obtained from children during ear surgery. Six specimens of normal adult auditory meatal skin served as control. Specimens were analyzed by immunohistochemistry using monoclonal antibodies with galectin-1 and galectin-3, and a polyclonal antibody with galectin-7. RESULTS: We did not observe any differences in the galectin distribution pattern between congenital and acquired pediatric cholesteatomas. Compared to the control group, cholesteatomas present some particular features. There was no expression of galectin-1 and a lower expression of galectin-3 in the epithelium. Furthermore, we observed a preferentially nuclear distribution of galectin-7 in cholesteatomas, whereas it is essentially cytoplasmic in the control group. CONCLUSION: The data reported in this study suggest, on the basis of a lesser marked galectin-3 in cholesteatomas epithelium compared with an external auditory canal skin, that an immature keratinocytes population is at the origin of these lesions and that galectin-3 and galectin-7 play a part in the capacity as apoptosis modulators. Our study does not establish a difference in the galectin expressions of congenital and acquired cholesteatomas, but it constitutes however an additional argument in favor of the "undifferentiated" origin of keratinocytes in cholesteatomas.
Adult ; Antibodies, Monoclonal ; Apoptosis ; Cell Proliferation ; Child ; Cholesteatoma ; Cholesteatoma, Middle Ear ; Cytoplasm ; Ear ; Ear Canal ; Epithelium ; Galectin 1 ; Galectin 3 ; Galectins ; Humans ; Immunohistochemistry ; Keratinocytes ; Lectins ; Skin

PURPOSE: The role of different galectins in the pathogenesis of different types of malignancy is now being intensely investigated. In this study, authors investigated the level of galectin-1 expression in human breast cancer tissue to define its relationship to the tumor invasiveness and tumor progression. METHODS: Formalin-fixed, paraffin-embedded tissues from 79 randomly selected breast cancer patients were used to perform immunohistochemical staining for galectin-1. The primary antibody was diluted mouse monoclonal antibody against galectin-1. The staining results were then interpreted by an experienced pathologist, and the results were compared between the groups having different pathologic variables. RESULTS: In breast cancer patients, galectin-1 was diversely expressed in the cancer tissue. Galectin-1 was expressed in both cancer cells and cancer-associated stromal cells. The levels of galectin-1 expression in cancer-associated stromal cells were higher in patients with invasive carcinoma (p = 0.001), in patients with advanced T stages (p = 0.007), and in patients with advanced TNM stages (p = 0.007). The galectin-1 expression in cancer-associated stromal cells was also higher in patients with lymph node metastasis and advanced N stages, but did not reach a statistically significant level. The galectin-1 expression in cancer cell did not have any correlation with pathologic variables. CONCLUSION: This is the first study that has demonstrated the relationship of galectin-1 expression with the tumor invasiveness and tumor progression in human breast cancer. Further large-scaled studies are needed to define the prognostic value of galectin-1 in breast cancer patients, and the exact role of galectin-1 should be investigated more thoroughly.
Animals ; Breast Neoplasms* ; Breast* ; Galectin 1* ; Galectins ; Humans* ; Immunohistochemistry ; Lymph Nodes ; Mice ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Stromal Cells

PURPOSE: The role of different galectins in the pathogenesis of different types of malignancy is now being intensely investigated. In this study, authors investigated the level of galectin-1 expression in human breast cancer tissue to define its relationship to the tumor invasiveness and tumor progression. METHODS: Formalin-fixed, paraffin-embedded tissues from 79 randomly selected breast cancer patients were used to perform immunohistochemical staining for galectin-1. The primary antibody was diluted mouse monoclonal antibody against galectin-1. The staining results were then interpreted by an experienced pathologist, and the results were compared between the groups having different pathologic variables. RESULTS: In breast cancer patients, galectin-1 was diversely expressed in the cancer tissue. Galectin-1 was expressed in both cancer cells and cancer-associated stromal cells. The levels of galectin-1 expression in cancer-associated stromal cells were higher in patients with invasive carcinoma (p = 0.001), in patients with advanced T stages (p = 0.007), and in patients with advanced TNM stages (p = 0.007). The galectin-1 expression in cancer-associated stromal cells was also higher in patients with lymph node metastasis and advanced N stages, but did not reach a statistically significant level. The galectin-1 expression in cancer cell did not have any correlation with pathologic variables. CONCLUSION: This is the first study that has demonstrated the relationship of galectin-1 expression with the tumor invasiveness and tumor progression in human breast cancer. Further large-scaled studies are needed to define the prognostic value of galectin-1 in breast cancer patients, and the exact role of galectin-1 should be investigated more thoroughly.
Animals ; Breast Neoplasms* ; Breast* ; Galectin 1* ; Galectins ; Humans* ; Immunohistochemistry ; Lymph Nodes ; Mice ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Stromal Cells

BACKGROUND: Galectin-1 (Gal-1) is a member of the galectin family of proteins, which are carbohydrate-binding proteins with an affinity for beta-galactosides. Gal-1 is differentially expressed by various normal and pathological tissues and it performs polyvalent, wide-ranging biological activities. A Gal-1 expression or over-expression in tumors and/or in the tissue surrounding them must be considered as a sign of malignant tumor progression that is often related to tumor metastasis. Although Gal-1 also plays important roles for tumorigenesis and tumor progression, the expression of Gal-1 in melanocytic nevus, dysplastic nevus and malgant melanoma has not yet been investigated. OBJECTIVE: We wanted to investigate and compare the expression of Gal-1 in melanocytic nevus, dysplastic nevusand malignant melanoma. METHODS: The paraffin-embedded specimens of 9 cases of malignant melanoma (MM), 6 cases of dysplastic nevus (DN) and 6 cases of intradermal nevus (IN) were subjected to immunohistochemical staining for Gal-1. RESULTS: The percentage of positive cells for Gal-1 in the MM was significantly higher than that of the DN and IN (p<0.01). The staining intensity of the positive cells for Gal-1 was the highest also in the MM. Meanwhile Gal-1 was more strongly expressed in highly atypical (more pleomorphic, more atypical mitoses) areas of the melanoma tissues. But there was no significant difference between the DN and IN for the expression of Gal-1. LIMITATION: This study is restricted to a small number of patients. CONCLUSION: The present study suggests that Gal-1 is more strongly expressed in malignant melanoma than in melanocytic nevus and dysplastic nevus. Interestingly, Gal-1 was more strongly expressed in the highly atypical portions of the melanoma tissue. Gal-1 might well contribute to the tumorigenesis and malignancy of melanocytes.
Benzamides ; Cell Transformation, Neoplastic ; Dysplastic Nevus Syndrome ; Galectin 1 ; Galectins ; Humans ; Melanoma ; Neoplasm Metastasis ; Nevus, Intradermal ; Nevus, Pigmented ; Proteins ; Tyrosine

Galectin-4 (Gal-4) is a β-galactoside-binding protein mostly expressed in the gastrointestinal tract of animals. Although intensive functional studies have been done for other galectin isoforms, the immunoregulatory function of Gal-4 still remains ambiguous. Here, we demonstrated that Gal-4 could bind to CD14 on monocytes and induce their differentiation into macrophage-like cells through the MAPK signaling pathway. Gal-4 induced the phenotypic changes on monocytes by altering the expression of various surface molecules, and induced functional changes such as increased cytokine production and matrix metalloproteinase expression and reduced phagocytic capacity. Concomitant with these changes, Gal-4-treated monocytes became adherent and showed elongated morphology with higher expression of macrophage markers. Notably, we found that Gal-4 interacted with CD14 and activated the MAPK signaling cascade. Therefore, these findings suggest that Gal-4 may exert the immunoregulatory functions through the activation and differentiation of monocytes.
Animals ; Antigens, CD14 ; Cell Differentiation ; Galectin 4 ; Galectins ; Gastrointestinal Tract ; Macrophages ; Monocytes ; Protein Isoforms

BACKGROUND: The decidua has been implicated in the “terminal pathway” of human term parturition, which is characterized by the activation of pro-inflammatory pathways in gestational tissues. However, the transcriptomic changes in the decidua leading to terminal pathway activation have not been systematically explored. This study aimed to compare the decidual expression of developmental signaling and inflammation-related genes before and after spontaneous term labor in order to reveal their involvement in this process. METHODS: Chorioamniotic membranes were obtained from normal pregnant women who delivered at term with spontaneous labor (TIL, n = 14) or without labor (TNL, n = 15). Decidual cells were isolated from snap-frozen chorioamniotic membranes with laser microdissection. The expression of 46 genes involved in decidual development, sex steroid and prostaglandin signaling, as well as pro- and anti-inflammatory pathways, was analyzed using high-throughput quantitative real-time polymerase chain reaction (qRT-PCR). Chorioamniotic membrane sections were immunostained and then semi-quantified for five proteins, and immunoassays for three chemokines were performed on maternal plasma samples. RESULTS: The genes with the highest expression in the decidua at term gestation included insulin-like growth factor-binding protein 1 (IGFBP1), galectin-1 (LGALS1), and progestogen-associated endometrial protein (PAEP); the expression of estrogen receptor 1 (ESR1), homeobox A11 (HOXA11), interleukin 1β (IL1B), IL8, progesterone receptor membrane component 2 (PGRMC2), and prostaglandin E synthase (PTGES) was higher in TIL than in TNL cases; the expression of chemokine C-C motif ligand 2 (CCL2), CCL5, LGALS1, LGALS3, and PAEP was lower in TIL than in TNL cases; immunostaining confirmed qRT-PCR data for IL-8, CCL2, galectin-1, galectin-3, and PAEP; and no correlations between the decidual gene expression and the maternal plasma protein concentrations of CCL2, CCL5, and IL-8 were found. CONCLUSIONS: Our data suggests that with the initiation of parturition, the decidual expression of anti-inflammatory mediators decreases, while the expression of pro-inflammatory mediators and steroid receptors increases. This shift may affect downstream signaling pathways that can lead to parturition.
Chemokines ; Cytokines ; Decidua ; Estrogen Receptor alpha ; Estrogens ; Female ; Galectin 1 ; Galectin 3 ; Galectins ; Gene Expression* ; Genes, Homeobox ; Humans ; Immunoassay ; Interleukin-8 ; Interleukins ; Leukocytes ; Membranes ; Microdissection ; Parturition* ; Plasma ; Pregnancy ; Pregnant Women ; Progesterone ; Real-Time Polymerase Chain Reaction ; Receptors, Progesterone ; Receptors, Steroid ; Sexual Development ; Transcriptome*

OBJECTIVETo evaluate the expression of galectin-3 and galectin-9 in mice nasal mucosa,and to explore the role of galectin-3 and galectin-9 in allergic rhinitis (AR).

METHODSTwenty mice were randomly divided into AR group and control group, 10 mice in each group. Ten mice of BALB/c were sensitized intraperitoneally with 10 microg of ovalbumin(OVA) adsorbed onto 2 mg Al(OH)3 on day 1 and day 14. Mice was induced daily by intranasal daily administration of 10 microl of saline containing 100 microg of OVA from day 21 to day 28. OVA was replaced with saline in control group. Immunohistochemical staining was used to examine the expression of galectin-3 and galectin-9 in nasal mucosa. RT-PCR was performed to investigate the level of mRNA expression of complement galectin-3, galectin-9. The level of IL-4, IL-5 and IFN-gamma in peripheral blood were titrated by ELISA.

RESULTSGalectin-3 and galectin-9 were detected in both groups. Expression of galectin-3 and galectin-9 in group AR was higher than that in control group. Pearson correlation analysis demonstrated that the levels of galectin-3 and galectin-9 were positively correlated with the level of IL-4 and IL-5, but negatively correlated with the level of IFN-gamma.

CONCLUSIONSGalectin-3 and galectin-9 might play an important role in the pathogenesis of allergic rhinitis.

Animals ; Female ; Galectin 3 ; metabolism ; Galectins ; metabolism ; Interferon-gamma ; blood ; Interleukin-4 ; blood ; Interleukin-5 ; blood ; Male ; Mice ; Mice, Inbred BALB C ; Nasal Mucosa ; metabolism ; Rhinitis, Allergic, Seasonal ; metabolism

Gastric cancer cells express large amounts of galectin-3 on the cell surface. This fact may provide the possibility to use galectin-3 protein as a surface target for delivering cytotoxic anticancer agents. To investigate the possibility of application of galectin-3 protein as a target protein in delivering cytotoxic anticancer agents, we synthesized doxorubicin immunoconjugate by using maleimidocaproic acid and conjugated doxorubicin immunoconjugate to anti-galectin-3 mAb. The anticancer effect of immunotoxin was assayed on NIH3T3, AGS and KATO III cell lines. The anticancer effect of immunotoxin on AGS cell line is highest and that of KATO III is higher than that of NIH3T3. This results relate to that of flow cytometry analysis previously shown and indicate that galectin-3 protein can be used as a target protein on the surface of gastric cancer cell for delivering cytotoxic anticancer agents.
Antineoplastic Agents* ; Cell Line ; Doxorubicin ; Flow Cytometry ; Galectin 3 ; Galectins* ; Immunoconjugates ; Immunotoxins ; Staphylococcal Protein A ; Stomach Neoplasms

PURPOSE: Galectin 3 is a beta-galactoside binding protein that is involved in various biological processes such as cell adhesion, migration, cell growth, tumor progression and metastasis. Although the precise acting mechanisms of Galectin 3 are unclear, it have been reported that the expression of Galectin 3 may related to tumor progression and metastasis. We investigated the immunohistochemical expression of Galectin 3 in 57 cases of benign and malignant breast neoplasm to evaluate the relation of a Galectin 3 expression to malignancy of breast neoplasm and the acting mechanism of Galectin 3. METHODS: Twenty fibroadenomas, 7 intraductal papillomas, 10 intraductal carcinomas and 20 invasive ductal carcinomas were studied. Immunostaining of Galectin 3 was evaluated in comparison with that of the internal controls, and the intensity of immunostaining was semiquantitatively graded on an intensity scale of 0 to 3. RESULTS: The normal ductal epithelium of the breast showed strong immunoreactivity with an intensity 2 to 3. The staining gradually and significantly decreased in accordance with the histopathological type and tumor progression from a fibroadenoma, intraductal papilloma, ductal carcinoma in situ and invasive ductal carcinoma (P<0.001). In particular, the expression of galection-3 was prominently decreased in invasive ductal carcinoma. CONCLUSION: The galectin-3 expression pattern suggests that progression from benign breast tumor to malignant breast tumor leads to a reduced expression of galectin-3.
Biological Processes ; Breast Neoplasms* ; Breast* ; Carcinoma, Ductal ; Carcinoma, Intraductal, Noninfiltrating ; Carrier Proteins ; Cell Adhesion ; Cell Movement ; Epithelium ; Fibroadenoma ; Galectin 3* ; Galectins* ; Neoplasm Metastasis ; Papilloma ; Papilloma, Intraductal