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ABSTRACT: Spectroscopic monitoring is applied to detect structural alterations for homodimeric adhesion/growth-regulatory galectins. Mammalian galectin-1 and the avian ortholog CG-1B, due to their distinct patterns of cysteine positioning, can undergo oxidation. When monitoring tryptophan fluorescence anisotropy comparatively, an indicator of structural changes affecting rotational diffusion, segmental motion and/or fluorescence life time, reductions are seen in both cases upon oxidation. The decrease was especially marked for the human protein, more than 2-fold compared to the avian lectin. Using this approach to analyze binding of lactose, equilibrium and kinetic binding constants of both proteins were similar. This result is corroborated by fluorescence correlation spectroscopy with labeled proteins. Of note, the diffusion constant of CG-1B increased by 5.6% in the presence of lactose, as has been seen for the human protein. When processing the other two homodimeric avian galectins (CG-1A, CG-2) accordingly it was revealed that sequence homology does not translate into identical behavior. The diffusion constant of CG-1A was not affected, a slight decrease (-3.8%) was observed for CG-2. Obviously, alterations induced by oxidation and responses to ligand binding are different between these closely related proteins. Methodologically, the two spectroscopic techniques are proven to be sensitive and robust sensors for detecting intergalectin differences.
Biochimie 08/2012; · 3.02 Impact Factor
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ABSTRACT: Previously, we found that treatment of cutaneous wounds with Atropa belladonna L. (AB) revealed shortened process of acute inflammation as well as increased tensile strength and collagen deposition in healing skin wounds (Gál et al. 2009). To better understand AB effect on skin wound healing male Sprague-Dawley rats were submitted to one round full thickness skin wound on the back. In two experimental groups two different concentrations of AB extract were daily applied whereas the control group remained untreated. For histological evaluation samples were removed on day 21 after surgery and stained for wide spectrum cytokeratin, collagen III, fibronectin, galectin-1, and vimentin. In addition, in the in vitro study different concentration of AB extract were used to evaluate differences in HaCaT keratinocytes proliferation and differentiation by detection of Ki67 and keratin-19 expressions. Furthermore, to assess ECM formation of human dermal fibroblasts on the in vitro level fibronectin and galectin-1 were visualized. Our study showed that AB induces fibronectin and galectin-1 rich ECM formation in vitro and in vivo. In addition, the proliferation of keratinocytes was also increased. In conclusion, AB is an effective modulator of skin wound healing. Nevertheless, further research is needed to find optimal therapeutic concentration and exact underlying mechanism of action.
Physiological research / Academia Scientiarum Bohemoslovaca 04/2012; 61(3):241-50. · 1.55 Impact Factor
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ABSTRACT: Lectin histochemistry has revealed cell-type-selective glycosylation. It is under dynamic and spatially controlled regulation. Since their chemical properties allow carbohydrates to reach unsurpassed structural diversity in oligomers, they are ideal for high density information coding. Consequently, the concept of the sugar code assigns a functional dimension to the glycans of cellular glycoconjugates. Indeed, multifarious cell processes depend on specific recognition of glycans by their receptors (lectins), which translate the sugar-encoded information into effects. Duplication of ancestral genes and the following divergence of sequences account for the evolutionary dynamics in lectin families. Differences in gene number can even appear among closely related species. The adhesion/growth-regulatory galectins are selected as an instructive example to trace the phylogenetic diversification in several animals, most of them popular models in developmental and tumor biology. Chicken galectins are identified as a low-level-complexity set, thus singled out for further detailed analysis. The various operative means for establishing protein diversity among the chicken galectins are delineated, and individual characteristics in expression profiles discerned. To apply this galectin-fingerprinting approach in histopathology has potential for refining differential diagnosis and for obtaining prognostic assessments. On the grounds of in vitro work with tumor cells a strategically orchestrated co-regulation of galectin expression with presentation of cognate glycans is detected. This coordination epitomizes the far-reaching physiological significance of sugar coding.
Histology and histopathology 04/2012; 27(4):397-416. · 2.48 Impact Factor
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T Grendel,
J Sokolský,
A Vaščáková,
V Hudák,
M Chovanec,
F Sabol,
S André,
H Kaltner, H-J Gabius,
M Frankovičová,
P Lenčeš,
J Betka,
K Smetana,
P Gál
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ABSTRACT: Tracheotomy may be associated with numerous acute and chronic complications including extensive formation of granulation tissue. The emerging functional versatility of the adhesion/growthregulatory galectins prompted us to perform a histochemical study of wound healing using rat trachea as model. By using non-cross-reactive antibodies and the labelled tissue lectins we addressed the issue of the presence and regulation of galectin reactivity during trachea wound healing. Beside localization of high-molecular-weight keratin, wide-spectrum cytokeratin, keratins 10 and 14, α-smooth muscle actin, vimentin, fibronectin, and Sox-2, galectins -1, -2, and -3 and their reactivity profiles were measured in frozen sections of wounded and control trachea specimens 7, 14, and 28 days after trauma. A clear trend for decreased galectin-1 presence and increased reactivity for galectin-1 was revealed from day 7 to day 28. Sox-2-positive cells were present after seven days and found in the wound bed. Interestingly, several similarities were observed in comparison to skin wound healing including regulation of galectin-1 parameters.
Folia biologica 01/2012; 58(4):135-43. · 1.15 Impact Factor
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ABSTRACT: The network of adhesion/growth-regulatory galectins in chicken (chicken galectin, CG) has only one tandem-repeat-type protein, CG8. Using a cell-based assay and probing galectin reactivity with a panel of fluorescent neoglycoconjugates (glycoprobes), its glycan-binding profile was determined. For internal validation, human galectin-8 (HG8) was tested. In comparison to HG8, CG8 showed a rather similar specificity: both galectins displayed high affinity to blood group ABH antigens as well as to 3'-sialylated and 3'-sulfated lactosamine chains. The most remarkable difference was found to be an ability of HG8 (but not CG8) to bind the disaccharide Galβ1-3GlcNAc (Le(c)) as well as branched and linear oligolactosamines. The glycan-binding profile was shown to be influenced by glycocalix of the cell, where the galectin is anchored. Particularly, glycosidase treatment of galectin-loaded cells led to the change of the profile. Thus, we suppose the involvement of cis-glycans in the interaction of cell-anchored galectins with external glycoconjugates.
Biochemistry (Moscow) 10/2011; 76(10):1185-92. · 1.06 Impact Factor
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ABSTRACT: Influenza virus is known to bind sialoglycans located on the surface of the host cell. In addition, recent data suggest the involvement of other molecular targets in viral reception. Of note, a high density of terminal galactose residues is created on the surface of virions because of the influenza virus' own neuraminidase activity. Thus, we suggested the possibility for an interaction of the influenza virus with galactose-binding proteins--galectins. In the present work we studied the influence of several galectins on the adhesion and further internalization of virus into the cell; six virus strains and three cell lines were studied. Chicken galectins CG-1A and -2 as well as human galectins HGal-1 and -8 promote virus binding in dose dependent manner, but they do not influence the internalization stage. Also, galectins are able to restore the ability of influenza virus to infect desialylated cells up to the level of native cells. When CG-1A in physiological concentrations was loaded onto viruses, the adhesion level was higher than in the case of on-cell loading. The effect of adhesion increase depends on the glycan structure of target-cell as well as of virus. The aggregated data suggest a promotional effect of galectins during the stage of influenza virus binding with the surface of target-cell.
Biochemistry (Moscow) 08/2011; 76(8):958-67. · 1.06 Impact Factor
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ABSTRACT: Nuclear galectins participate in splicing of pre-mRNA. In this study we detected galectins-1, -2, -3 and -7 and their glycoligands in three types of cells: fibroblasts, cancer epithelial cells and melanoma cells. The results demonstrated that the nuclear expression of distinct types of galectins and their ligands in interphasic nuclei is dependent on the cell type. The extensive binding of labelled galectins-1 and -2 to mitotic cells (around chromosomes, in mitotic spindle and in bridge connecting both daughter cells) suggests their role during the cell division.
Folia biologica 01/2011; 57(3):125-32. · 1.15 Impact Factor
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ABSTRACT: The emerging insights into glycan functionality direct increasing attention to monitor core modifications of N-glycans and branch-end structures. To address this issue in histochemistry, a panel of lectins with respective specificities was devised. The selection of probes with overlapping specificities facilitated to relate staining profiles to likely target structures. The experiments on fixed sections of adult murine testis and epididymis were carried out at non-saturating lectin concentrations to visualize high-affinity sites with optimal signal-to-background ratio. They revealed selectivity in lectin reactivity for distinct cell types and segment-dependent staining in the epididymis. Leydig cells, for instance, were reactive with the Sambucus nigra agglutinin and human siglec-2 (CD22), two lectins also separating principal from basal and apical cells in the caput segments I-III of the epididymis. Apical cells were reactive with the Maackia amurensis agglutinin-I, and basal cells with the erythroagglutinin of Phaseolus vulgaris. The reported differences support the concept of lectin staining as cell marker. They thus intimate to study glycogene (genes for glycosyltransferases and lectins) expression and cellular reactivity with tissue lectins. These investigations will be instrumental to assign a role as biochemical signals to the detected staining properties.
Anantomia Histologia Embryologia 12/2010; 39(6):481-93. · 0.90 Impact Factor
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Sven Saussez,
Laurence de Leval,
Christine Decaestecker,
Nicolas Sirtaine,
Stéphanie Cludts,
Anaelle Duray,
Dominique Chevalier,
Sabine André, Hans-Joachim Gabius,
Myriam Remmelink,
Xavier Leroy
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ABSTRACT: Warthin's tumor of the parotid gland is assumed to originate from the proliferation of epithelial inclusions within parotid lymph nodes. In that case, these cells are supposed to retain characteristics similar to common salivary gland ductal cells. Using immunohistochemical fingerprinting with four members of the family of adhesion/growth-regulatory galectins and comparison to intra- and interlobular ducts, marked similarities were noted for presence of galectins-3, -7 and -8. Notably, profiles of lectin binding, determined by applying human lectins as probes, were also similar when testing biotinylated galectins-3 and -8. Besides defining the galectin histochemical parameters in Warthin's tumors this study adds support to the hypothesis of heterotopia.
Histology and histopathology 05/2010; 25(5):541-50. · 2.48 Impact Factor
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ABSTRACT: We have recently shown that the carbohydrate-binding pattern of galectins in cells differs from that determined in artificial (non-cellular) test-systems. To understand the observed discrepancy, we compared several test-systems differing in the mode of galectin presentation on solid phase. The most representative system was an assay where the binding of galectin (human galectins-1 and -3 were studied) to asialofetuin immobilized on solid phase was inhibited by polyacrylamide glycoconjugates, Glyc-PAA. This approach permits us to range quantitatively glycans (Glyc) by their affinity to galectin, i.e. to study both high and low affinity ligands. Our attempts to imitate the cell system by solid-phase assay were not successful. In the cell system galectin binds glycoconjugates by one carbohydrate-recognizing domain (CRD), and after that the binding to the remaining non-bound CRD is studied by means of fluorescein-labeled Glyc-PAA. In an "imitation" variant when galectins are loaded on adsorbed asialofetuin or Glyc-PAA followed by revealing of binding by the second Glyc-PAA, the interaction was not observed or glycans were ordered poorly, unlike in the inhibitory assay. When galectins were adsorbed on corresponding antibodies (when all CRDs were free for recognition by carbohydrate), a good concentration dependence was observed and patterns of specificities were similar (though not identical) for the two methods; notably, this system does not reflect the situation in the cell. Besides the above-mentioned, other variants of solid-phase analysis of galectin specificity were tested. The results elucidate the mechanism and consequence of galectin CRD cis-masking on cell surface.
Biochemistry (Moscow) 03/2010; 75(3):310-9. · 1.06 Impact Factor
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ABSTRACT: Benign and malignant fibrous histiocytoma present with a considerable difference concerning cellular organization in their vicinity.
Normally appearing epithelium covers the malignant form in contrast to hyperplastic epidermis for benign tumors. It is an open question as to whether the tumor-associated fibroblasts are capable to affect phenotypic features of normal keratinocytes, prompting this comparative analysis.
Fibroblasts were isolated from benign and malignant fibrous histiocytomas, respectively, and also from normal dermis. The resulting cell populations were thoroughly characterized immunocytochemically using a large panel of antibodies. The three fibroblast preparations were cocultured with normal interfollicular keratinocytes. Their phenotype was characterized for distinct properties including differentiation and proliferation.
Fibroblasts prepared from both tumor types were phenotypically practically identical with normal dermal fibroblasts. Their activities on keratinocytes were different. Cells prepared from benign fibrous histiocytoma were capable to effect strong expression of keratin 19 and production of a galectin-1-rich extracellular matrix. Fibroblasts isolated from malignant fibrous histiocytoma led to a phenotype very similar to that when keratinocytes were cocultured with normal dermal fibroblasts.
Fibroblasts prepared from benign fibrous histiocytoma were biologically active on keratinocytes in a particular manner. Our results on fibroblast activity are suggested to be relevant for morphologic differences observed in vivo between normal epidermis and epidermis adjacent to the studied tumor types.
Journal of dermatological science 06/2009; 55(1):18-26. · 3.71 Impact Factor
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Z Cada,
M Chovanec,
K Smetana,
J Betka,
L Lacina,
J Plzák,
R Kodet,
J Stork,
M Lensch,
H Kaltner,
S André, H-J Gabius
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ABSTRACT: The human lectin galectin-7 (Gal-7; p53-induced gene-1) has anti- and pro-malignant features in different in vitro models. We tried to clarify relation of its expression to cellular and clinical parameters in head and neck squamous and basal cell carcinomas. Using a non-cross-reactive antibody, immunohistochemical staining in squamous cell epithelia (epidermis, epithelium of oropharynx and larynx) (n = 57), squamous cell carcinomas (n = 47) and lymph node metastases (n = 25), as well as basal cell carcinomas (n = 10) were studied. This monitoring was flanked by processing to assess the level of differentiation (cytokeratins 10 and 14), proliferation (Ki67) and basal lamina formation (collagen IV). The results were correlated with clinical and pathological findings (grading, TNM-staging, extracapsular spread, angio- and lymphangioinvasion, perineural invasion, recurrence and survival). Gal-7 resides in all layers of epithelia with cytoplasmic and nuclear localization in normal specimens. Basal cell carcinomas were devoid of the Gal-7 respective signal. Squamous cell carcinomas were positive, presenting different staining profiles. Intense staining was predominantly found in squamous cell cancers with high degrees of differentiation and keratinization. Fittingly, poor level of differentiation (P = 0.0009), absence of keratinization (P = 0.0105) and significant discontinuity or absence of collagen IV expression in the peritumoral basal lamina (P = 0.0024) was found in Gal-7-negative tumors. Gal-7 presence was not related to gender, primary tumor site, T-stage, N-stage, clinical stage, extracapsular spread, angio- and lymphangioinvasion, perineural spread or treatment outcome at a statistically significant level. Immunohistochemical analysis revealed a positive correlation for differentiation and keratinization to Gal-7 presence in squamous cell carcinomas. Absence of Gal-7 expression was detected in basal cell carcinomas. These clinical data delineate Gal-7 influence on differentiation in vivo, without evidence for a role in dissemination reported for lymphoma.
Histology and histopathology 02/2009; 24(1):41-8. · 2.48 Impact Factor
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ABSTRACT: Glycans of natural glycoconjugates are considered as a source of biological information relevant to cell adhesion or growth. Sugar-based messages are decoded and translated into responses by endogenous lectins. This mechanism assigns a functional dimension to tumour-associated changes of glycosylation. Consequently, it calls for mapping the lectin presence in tumours. Such an analysis has so far commonly been performed with the scope to determine expression of a few distinct proteins, e.g. from the effector family of galectins with focus on galectins-1 and -3. Due to the emerging evidence for functional divergence among galectins it is timely to address the challenge to evaluate their presence beyond these few family members. Having raised a panel of non-cross- -reactive antibodies against seven human galectins covering all three subfamilies, we de scribe their expression profiles in human skin. Comparison of normal and malignant tissues enabled us to define galectin-type-dependent alterations, arguing in favour of distinct functionalities. It is concluded that comprehensive monitoring performed to define the different aspects of the galectin network, as documented in this pilot study, is advisable for future histopathologic studies aimed at delineating clinical correlations.
Folia biologica 02/2009; 55(4):145-52. · 1.15 Impact Factor
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J Klíma,
L Lacina,
B Dvoránková,
D Herrmann,
J W Carnwath,
H Niemann,
H Kaltner,
S André,
J Motlík, H-J Gabius,
K Smetana
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ABSTRACT: The glycophenotyping of mammalian cells with plant lectins maps aspects of the glycomic profile and disease-associated alterations. A salient step toward delineating their functional dimension is the detection of endogenous lectins. They can translate sugar-encoded changes into cellular responses. Among them, the members of the lectin family of galectins are emerging regulators of cell adhesion, migration and proliferation. Focusing on galectins-1, -3 and -7, we addressed the issue whether their expression is regulated during wound healing in porcine skin as model. A conspicuous upregulation is detected for galectin-1 in the dermis and a neoexpression in the epidermis, where an increased level of galectin-7 was also found. Applying biotinylated tissue lectins as probes, the signal intensities for accessible binding sites decreased, intimating an interaction of the cell lectin with reactive sites. In contrast, galectin-3 parameters remained rather constant. Of note, epidermal cells in culture also showed an increase in expression/presence of galectin-1, measured on the levels of mRNA and protein, in this case by Western blotting and quantitative immunocytochemistry. Used as matrix, galectin-1 conferred resistance to trypsin treatment to attached human keratinocytes and reduced migration into scratch-wound areas in vitro. This report thus presents new information on endogenous lectins in wound healing and differential regulation among the three tested cases.
Physiological research / Academia Scientiarum Bohemoslovaca 01/2009; 58(6):873-84. · 1.55 Impact Factor
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ABSTRACT: The enzymatic activity of matrix metalloproteinase-9 (MMP-9) suggests that its presence in hypopharyngeal and laryngeal squamous cell carcinomas (HSCCs, LSCCs) could have prognostic value. We tested this hypothesis by quantitative morphometric analysis of immunohistochemical staining in histological sections of 73 stage IV HSCCs and 45 LSCCs (30 cases of stage I/II, 15 cases of stage IV). As compared to tumour-free epithelium an increase for the labelling index in LSCCs reached statistical significance (p=0.04). Specimens of Reinke's edema were strongly higher in this parameter compared to tumour-free tissue area (p=0.000001), underscoring an association between the level of MMP-9 expression and inflammation. Focusing on patients' recurrence status we identified thresholds for the labelling index of 10% for HSCCs and 18% for LSCCs, both indicating rapid recurrence and dismal prognosis unless surpassed. When relating data for MMP-9 to those for three adhesion/growth-regulatory galectins, a positive correlation with galectin-7 expression was detected in LSCCs. This finding suggests a possible potential role of this endogenous lectin as inducer of MMP-9 gene expression in situ. Of note, galectin-1 expression was negatively correlated with MMP-9 and that of galectin-3, a substrate of MMP-9, not related. In conclusion our study delineated a prognostic role of MMP-9 immunodetection in high-stage HSCCs and in LSCCs when separating patients by a distinct threshold for the labelling index. Moreover, it indicated associations between MMP-9 and multifunctional galectins-1 and -7 in situ.
Int J Oncol. 01/2009; 34(2):433-9.
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ABSTRACT: BACKGROUND: Galectin-1 has been found to modulate lymphocyte invasion in inflammation and to be involved in angiogenesis in models, thus prompting examination of its clinical relevance in laryngeal cancer. PATIENTS AND METHODS: Immunohistochemical processing of tissue sections (n=53) from patients with stage I/II (n=35) and stage IV (n=18) laryngeal squamous cell carcinoma (LSCC) with a specific anti-galectin-1 antibody and monitoring of CD45/CD31 positivity was combined with quantitative morphometric analysis. RESULTS: Lectin presence in the tumor and endothelial cells was positively correlated, while a negative relationship to the number of CD45-positive lymphocytes was demonstrated. No association was seen with the extent of neovascularization. The mean optical density (MOD) of lectin-dependent staining in the tumor stroma was significantly increased compared to normal stroma. CONCLUSION: Galectin-1 was not associated with angiogenesis in the studied cohort while galectin-1 in endothelial cells may negatively influence lymphocyte invasion and the mean optical density for the stromal galectin-1 signal is up-regulated in tumors.
Anticancer Res. 01/2009; 29(1):59-65.
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ABSTRACT: The human lectin galectin-3 is a multifunctional effector with special functions in regulation of adhesion and apoptosis. Its unique trimodular organization includes the 12-residue N-terminal sequence, a substrate for protein kinase CK1-dependent phosphorylation. As a step towards elucidating its significance, we prepared phosphorylated galectin-3, labelled it and used it as a tool in histochemistry. We monitored normal and malignant squamous epithelia. Binding was suprabasal with obvious positive correlation to the degree of differentiation and negative correlation to proliferation. The staining pattern resembled that obtained with the unmodified lectin. Basal cell carcinomas were invariably negative. The epidermal positivity profile was akin to distribution of the desmosomal protein desmoglein, as also seen with keratinocytes in vitro. In all cases, binding was inhibitable by the presence of lactose, prompting further investigation of the activity of the lectin site by a sensitive biochemical method, i.e. isothermal titration calorimetry. The overall affinity and the individual enthalpic and entropic contributions were determined. No effect of phosphorylation was revealed. This strategic combination of histo- and biochemical techniques applied to an endogenous effector after its processing by a protein kinase thus enabled a detailed monitoring of the binding properties of the post-translationally modified lectin. It underscores the value of using endogenous lectins as a histochemical tool. The documented approach has merit for applications beyond lectinology.
Anantomia Histologia Embryologia 11/2008; 38(1):68-75. · 0.90 Impact Factor
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ABSTRACT: To examine the level of expression of the pleiotropic regulators galectins-1 and -7 in relation to neoplastic progression of hypopharyngeal (HSCCs) and laryngeal (LSCCs) squamous cell carcinomas.
The presence of galectins-1 and -7 was investigated using quantitative immunohistochemistry in (i) a series of 78 HSCCs by comparison with 17 normal epithelia (N_E), 26 low-grade dysplasia (low_D) and 27 high-grade dysplasia (high_D) and (ii) a series of 56 LSCCs by comparison with 50 N_E, 23 low_D and 29 high_D. Galectin-1 positivity expressed as a percentage of cells was significantly higher in carcinomas (HSCCs and LSCCs) than in N_E, low_D or high_D (P < 10(-6)). Galectin-7 expression was elevated in low_D (P = 0.0004) compared with N_E and in carcinomas (HSCC) compared with high_D (P = 0.0002). Tumour progression from high_D to carcinomas was associated with a shift of galectin-1 localization from the nucleus towards the cytoplasm. Increased expression of galectin-7 in dysplasias was accompanied by a shift from the cytoplasmic compartment (N_E) to the nucleus (low_D and high_D).
Our data reveal an association between the level of presence of galectins-1 and -7 and neoplastic progression of HSCCs and LSCCs. Moreover, inverse shifts between nuclear and cytoplasmic positivity intimating functional divergence were detected.
Histopathology 04/2008; 52(4):483-93. · 3.08 Impact Factor
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ABSTRACT: Galectins have the particular capacity to interact with distinct proteins, in addition to the typical reactivity of lectins with glycans. Therefore, they can be functionally active when residing at places other than the membrane or extracellular matrix. In fact, nuclear presence of galectins-1 and -3 is solidly documented but it is an open question whether these two cases are exceptional within this lectin family. Thus, galectin-2, which shares 43% sequence identity on the protein level with galectin-1, warrants study in this respect. Based on initial immunohistochemical evidence we herein address the issue as to whether this galectin can join the category of nuclear lectins. To do so we studied different types of cell in vitro using an antibody preparation free of cross-reactivity against other tested galectins. The immunocytochemical experiments revealed that galectin-2 was present in nuclei of murine 3T3 fibroblasts and also genetically engineered human colon carcinoma cells with stable ectopic expression. Transport of galectin-2 to the nucleus could be enhanced by physical (UV light), chemical (mitomycin C, serum withdrawal) or cell biological (coculture with stromal cells) treatment modalities. As a means of further characterizing the staining profile cytochemically, a series of markers with well-defined site of residency within the nuclear compartment was tested in parallel. Importantly, no colocalization with galectins-1 and -3 and the splicing factor SC35 was detectable, the former cases also serving as inherent specificity control. In contrast, a similarity was uncovered in the case of the promyelocytic leukemia (PML) protein as marker of PML nuclear bodies. In aggregate, nuclear localization is documented for galectin-2. This attribute should thus not be considered as an exceptional finding confined to galectins-1 and -3. That even closely related family members, here galectins-1 and -2, exhibit distinct intranuclear localization patterns gives ensuing research a clear direction.
Histology and histopathology 03/2008; 23(2):167-78. · 2.48 Impact Factor
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S Langbein,
J Brade,
J K Badawi,
M Hatzinger,
H Kaltner,
M Lensch,
K Specht,
S André,
U Brinck,
P Alken, H-J Gabius
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ABSTRACT: Lectins, and especially galectins, appear to be important in malignancy-associated processes. The aim was to analyse comprehensively the presence of galectins in urothelial tumours.
Non-cross-reactive antibodies against seven family members from the three subgroups (prototype: galectin-1, -2 and -7; chimera type: galectin-3; tandem-repeat type: galectin-4, -8 and -9) were used. Gene expression was monitored in specimens of normal urothelium, fresh tumour tissue and cell lines by real-time polymerase chain reaction (PCR). The presence and evidence of tumour-associated up-regulation were shown for galectin-1 and -3. This was less clear-cut for galectin-4 and -8. Galectin-7 was expressed in all cell lines; galectin-2 and -9 were detected at comparatively low levels. Galectin-2, -3 and -8 up-regulation was observed in superficial tumours, but not in muscle-invasive tumours (P < 0.05). Immunoreactivity correlated with tumour grading for galectin-1, -2 and -8, and disease-dependent mortality correlated with galectin-2 and -8 expression. Binding sites were visualized using labelled galectins.
The results demonstrate a complex expression pattern of the galectin network in urothelial carcinomas. Galectin-1, -2, -3 and -8 are both potential disease markers and also possible targets for bladder cancer therapy.
Histopathology 11/2007; 51(5):681-90. · 3.08 Impact Factor
