Biomedical subjects

H J Gabius

Publications and source records attributed to H J Gabius.

At least 163 records · Page 9Linked to original sources

PubMed1995

Quantitative differences in neoglycoprotein binding for vascular endothelial cells from porcine brain, ovary, and testis in vitro.

Carrier-immobilized carbohydrates are valuable tools for assessing the glycoligand-binding capacity of cell surfaces. A panel of 10 types of fluorescent neoglycoproteins has been synthesized to determine the extent of their specific binding to endothelial cells in vitro that have been obtained from porcine brain, ovary, and testis. Different sugar moieties revealed a nonuniform capacity to bind to the endothelial cells as determined by flow cytometric analysis, the histogenetic origin of the preparations being an important factor. Binding of mannose, xylose, and glucuronic acid was especially pronounced, but the extent of cell-associated fluorescence was significantly different dependent on the source of the endothelial cells. These results clearly reveal that endothelial cells in vitro display the capacity to specifically recognize defined carbohydrate moieties. Moreover, endothelial cells of different tissue origin can exhibit variability in this property, potentially endowing this cell type with site-dependent molecular properties.

Animals↗

PubMed1995

Characterization of sugar receptor expression by neoglycoproteins in oral and oropharyngeal squamous cell carcinomas.

Recognition of the carbohydrate part of cellular glycoconjugates by sugar receptors like lectins may contribute to biosignaling and interactions between normal and transformed cells. Such recognitions may be essential for establishing phenotypic characteristics in neoplastic cells, including metastasis-associated properties. To evaluate various glycoconjugates in tumor diagnosis and clinical therapy, a panel of 18 biotinylated neoglycoproteins was prepared. This included conjugates of a histochemically inert carrier protein and crucial sugar moieties such as D-glucuronic acid, alpha- and beta-N-acetyl-galactosamine, beta-N-acetyl-glucosamine, melibiose, lactose, maltose, cellobiose, mannose, mannose-6-phosphate, fucose, rhamnose, and xylose. In so doing the diazo derivative of the respective p-aminophenyl glycosides was coupled with galactose, beta-N-acetyl-galactosamine or beta-N-acetyl-glucosamine via an epoxy group-containing aliphatic spacer. Other glycoconjugates used were the proteoglycan heparin and the sulfated fucan fucoidan. Labeling was effected with cyanogen bromide activation and aminoalkylation for specific detection of endogeneous sugar receptors, especially lectins. Tissues studied were paraformaldehyde-fixed, paraffin-embedded surgical biopsies from patients with different stages of squamous cell carcinomas (SCCs) of the oral cavity (n = 16) and oropharynx (n = 17), including three lymph node metastases from oropharyngeal primary tumors. Semiquantitative binding differences of probes to tumor stages were evaluated statistically by the Mann-Whitney U-Wilcoxon rank sum W test. Specific binding of a probe to cytoplasmic and nuclear structures was detected with apparent quantitative differences. Overall, the cytoplasmic compartment revealed a higher intensity of histochemical reaction than did nuclear structures, indicating a comparatively higher density of specific carbohydrate receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1995

Characterization of glycoconjugate expression during development of Meckel's cartilage in the rat.

The staining patterns of 24 biotinylated lectins were analyzed in serial sections of the mandible of 13- to 21-day-old rat embryos by means of the avidin-biotin-peroxidase method. A ubiquitous distribution of binding sites was demonstrated after incubation with Con A (Canavalia ensiformis), DSL (Datura stramonium; except bone matrix), and WGA (Triticum vulgare). ECL (Erythrina cristagalli), GSL I (Griffonia simplicifolia), SJA (Saphora japonica), VVL (Vicia villosa), DBA (Dolichus biflorus), UEA I (Ulex europeus), and LTA (Lotus tetragonobolus) were constantly negative. In early stages of development, GSL II (Griffonia simplicifolia II) was a selective marker of prechondral blastema. In contrast, PNA (Arachis hypogaea) did not stain condensing mesenchyme. During chondrogenesis of Meckels's cartilage a general decrease of lectin binding was observed. Mature cartilage matrix was constantly negative. Chondrocytes were marked by the lectins PSA (Pisum sativum), WGA, PHA-E, and PHA-L (Phaseolus vulgaris E and L). A strong GSL II binding was restricted to the mesial-superior region of the perichondrium. In later stages, several lectins revealed significant differences between preskeletal ("central") areas and the remaining ("peripheral") mesenchyme. A clear binding reaction was noted in central regions by applying LEA (Lycopersicon esculentum) and STL (Solanum tuberosum), while the peripheral tissue was only faintly stained. Developing bone was specifically marked by succinylated WGA (sWGA). The lectins LCA (Lens culinaris) and RCA (Ricinus communis) bound to fibers and extracellular matrix of the connective tissue. Jacalin (Artocarpus integrifolia) and SBA (Glycine max) binding sites were found in macrophages. Affinity of VAA (Viscum album) increased parallel with maturation of endothelial cells. Specific lectin-binding patterns revealed no correlation with the distribution of glycosaminoglycans. The results demonstrate a general reduction of oligosaccharide structures during development of Meckel's cartilage. From our observations we conclude that intralaminar glucose and/or mannose sequences as well as terminal sialic acid molecules are ubiquitously distributed, while terminal alpha-fucose was constantly negative. Lectin-binding patterns of macrophages may reflect the presence of specifically linked terminal galactose. Our findings indicate that oligosaccharides terminating in N-acetylglucosamine are bone-specific. The significance of the restricted staining of the perichondrium by GSL II remains to be elucidated.

Animals↗

PubMed1995

Carbohydrate-binding proteins (plant/human lectins and autoantibodies from human serum) as mediators of release of lysozyme, elastase, and myeloperoxidase from human neutrophils.

Analysis of cell surface glycosylation not only provides information about cell properties such as their state of differentiation or histogenetic lineage. The carbohydrate chains also provide potentially functional binding sites to endogenous carbohydrate-binding proteins. This interaction can elicit consequent signalling processes. Because of the importance of neutrophils in the host defence system, we monitored the effect of the binding of such sugar receptors to their cell surface on the release of the enzymatic activities of lysozyme, elastase, and myeloperoxidase. Besides the mannose-binding lectin concanavalin A and the immunomodulatory alpha/beta-galactoside-binding lectin from Viscum album L., three preparations of human sugar receptors - beta-galactoside-binding lectin (M(r) 14 kDa) and two affinity-purified polyclonal IgG fractions from serum with the capacity to recognize alpha- or beta-galactosides, respectively - were used. Two animal lectins from chicken liver and intestine that bind beta-galactosides, as well as the lectin-like human serum amyloid P component, were included in order to assess the importance of slight differences in ligand recognition. Cytochalasin B-enhanced enzyme release was invariably seen with the two plant lectins and the chicken liver beta-galactoside-binding lectin, but the related intestinal lectin did not increase enzyme release. The mammalian homologue of these avian lectins triggered lysozyme secretion, and the lactoside-binding IgG fraction enhanced the amount of extracellular elastase activity slightly but significantly. Thus, the actual lectin, not the nominal specificity of sugar receptors, is crucial for elucidation of responses. Due to the highly stimulatory activity of the two plant lectins, neutrophils from patients with non-cancerous diseases and from patients with lung cancer were monitored for the extent of lectin-mediated enzyme release. Only the concanavalin A-mediated reactivity of the neutrophils was associated with the type of disease.

Adult↗

PubMed1995

Mapping of endogenous lectins in macrophages colonizing an implanted polymer surface--effect of polymer structure.

The design of synthetic polymers may affect structural features of inflammatory cells, for example the expression of endogenous sugar receptor molecules like lectins in macrophages and foreign body giant multinucleate cells. This characteristic was studied histochemically by use of biotinylated (neo)glycoproteins. The results demonstrate the influence of polymer structure on the phenotypic expression of molecules recognizing carbohydrates in these cells. Very strong activity was observed for carrier-immobilized beta-galactose in cells colonizing hydrophobic polystyrene implants. Sialic acid moieties were not recognized by cells located on the surface of all types of polymeric implant. This study encourages investigation of the influence of polymer design on the differentiation of macrophages.

Animals↗

PubMed1995

Viscum album agglutinin-induced aggregation of blood cells and the lectin effects on neutrophil function.

Extracts from mistletoe enjoy a large popularity in central Europe as an unconventional treatment modality for cancer, warranting scientific efforts with defined components to delineate any potential benefit. The galactose-specific lectin from Viscum album (VAA), known to exhibit immunomodulatory and ensuing antitumoral capacities in animal model systems, was shown to aggregate human blood cells in the following order: neutrophils, mononuclear cells--thrombocytes and erythrocytes. To contribute to the analysis of lectin effects on individual aspects of the host defence system, two parameters of neutrophils were quantitatively assessed, namely the aggregating activity of VAA as a measure of strength of interaction with cell surface ligands and the effect of lectin on oxidative metabolism (H2O2 release) of these cells. It was found that whole lectin and its carbohydrate-binding B-subunit possessed the capacity to induce cell aggregation and H2O2 release, which were blocked by D-galactose and lactose. Both effects displayed similar dependence on the lectin concentration in the range 0.1-25 micrograms/ml. The toxic A-subunit displayed detectable activity only in high doses (50 micrograms/ml) while the bovine heart galaptin (14 kDa; galectin-1) failed to affect neutrophils. The role of oxidative metabolism in regulation of neutrophil aggregation induced by VAA was studied using metabolic inhibitors and controlled heating at 46 degrees C leading to inhibition of plasma membrane NADPH-oxidase system. Trifluoperazine and menadione inhibited the neutrophil aggregation in a dose-dependent manner in comparison with such inhibitors as amiloride and theophylline.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Cells↗

PubMed1995

Differential expression of calcyclin and its accessible ligands in various types of cutaneous tumors.

Calcyclin is the product of a gene that is regulated in dependence of the cell cycle in fibroblasts in vitro. It has recently been proven to be a sialic acid-binding protein in vitro and in the case of mammalian tissues to bind specifically to annexin II, annexin VI, annexin XI, and glyceraldehyde-3-phosphate dehydrogenase in a Ca(2+)-dependent manner. Since calcyclin can be labelled without impairment of its binding activity, it can be employed as a histochemical tool to localize its accessible ligands. Concomitantly, immunohistochemical localization of calcyclin with a specific antibody is warranted. By using histochemical and immunohistochemical techniques, the expression of calcyclin and its accessible binding sites are demonstrated in serial sections of normal skin and benign, pre-cancerous and malignant tumors of the skin, namely in verruca vulgaris, papillary hidradenoma, syringoma, keratoacanthoma, Bowen's disease, squamous cell carcinoma, melanocytic naevi, primary and metastatic malignant melanoma and non-Hodgkin lymphoma (NHL) of the skin. Cytoplasmic and nuclear expression of calcyclin and its ligands is unexceptionally found in normal skin, epithelial tumors and benign melanocytic tumors. Presence of calcyclin and calcyclin-binding sites is detected in more than 80% of tumor cells in the epithelial lesions. In the group of melanomas and lymphomas heterogeneity is obvious. The application of annexin-specific antibodies raises evidence that members of this protein family co-localize with calcyclin in situ to some extent. These findings suggest that calcyclin and accessible calcyclin-binding molecules, like certain annexins, may be differentially regulated in melanomas and lymphomas in contrast to epithelial lesions with presently undefined biological implications.

Annexins↗

PubMed1995

Estrous cycle-related alterations in the expression of glycoconjugates and lectins in the mouse endometrium shown histochemically.

Alterations of the hormonal status may influence diverse cell features relevant to intra- and intercellular communication. We studied histochemically the expression of glycans and endogenous sugar-binding proteins (endolectins) in the mouse endometrium during the estrous cycle. The avidin-biotin-peroxidase complex (ABC) technique was used on paraffin sections with a panel of biotinylated lectins and neoglycoproteins. Stage-specific changes were observed with Galanthus nivalis agglutinin (GNA), Ulex europaeus-I agglutinin (UEA-1), Sambucus nigra agglutinin (SNA), Ricinus communis agglutinin (RCA-I) and Glycine max agglutinin (SBA) in both the luminal and the glandular epithelium, but to a lesser extent in the latter. The stromal constituents also exhibited modifications in lectin-binding profiles in cyclic mice. In addition to the analysis of cell glycans endogenous carbohydrate-binding sites were studied using synthetic probes, biotinylated neoglycoproteins. These tools made it possible to conclude that hormonal status can affect the expression of endolectins. We have attempted to correlate the glycohistochemical findings with recently published data obtained biochemically. The results indicate that phase-specific alterations in lectin-binding glycoproteins and endolectins occur in the endometrium of mice associated with their short reproductive cycle.

Animals↗

PubMed1995

Influence of the galactoside-specific lectin from Viscum album and its subunits on cell aggregation and selected intracellular parameters of rat thymocytes.

Galactose-specific lectin from Viscum album (VAA) was shown to induce the aggregation of rat thymocytes, to increase the intracellular Ca(2+)-availability, and to enhance the menadione-dependent release of H2O2 from cells in a carbohydrate- and dose-dependent manner. This activity was mediated by the carbohydrate-binding B-subunit, whereas the toxic A-subunit failed to display aggregating activity or to affect the intracellular Ca2+. However, incubation of cells in its presence decreased the release of H2O2. These data extend the knowledge of the immunomodulatory potency of VAA, especially its carbohydrate-binding B chain.

Animals↗

PubMed1995

Distribution patterns of neoglycoprotein-binding sites (endogenous lectins) and lectin-reactive glycoconjugates during cartilage and bone formation in human finger.

The distribution of endogenous lectins, visualized by labelled neoglycoproteins, and of defined oligosaccharide structures, reactive with plant lectins, during fetal development of the fingers was analyzed in sections of human 3- to 8-month-old fetal specimens. Chondrogenesis as well as ossification were correlated with characteristic modulations in the expression of both glycoligand-binding molecules and characteristic carbohydrate structures. Occurrence of xylose-specific receptors was judged to be an early sign of cartilage development. Similarly, alpha-mannosyl residues that had been attached to labelled carrier proteins were strongly bound by the extracellular matrix already during early stages of finger maturation. Staining intensity for heparin gradually increased during chondrogenesis, whereas affinity for mannose showed a stage-related decline. Binding of mannose-6-phosphate was confined to hypertrophied cartilage of primary ossification centers. Accessible binding sites for terminal N-acetylneuraminic acid and N-acetylgalactosamine moieties were detected only in osteoid. In addition to monitoring the sugar-binding capacity, presence and developmental regulation of distinct carbohydrate structures were also assessed. PSA and SBA enabled the demonstration of an abrupt loss of staining affinity in the zone of maturing hypertrophic cartilage. Succinylated WGA proved to be an apparently useful marker of evolving bone tissue. GSL-II binding was restricted to chondroclasts and osteoclasts. The findings of this investigation are consistent with the supposed role of glycoconjugate-lectin interactions in cartilage and bone development.

Binding Sites↗

PubMed1995

Necrotizing bronchitis, angiitis, and amyloidosis associated with chronic Q fever.

The authors report the clinical, radiological and histological findings in a 63-year-old male patient who developed severe necrotizing bronchitis, necrotizing angiitis, and secondary amyloidosis of the right upper love and intermediate bronchus. The patient expired due to respiratory insufficiency. At the age of 27 years, the patient had had radiotherapy of the mediastinum because of suspected Hodgkin's disease. Acute pneumonia suggestive of Q-fever infection was diagnosed at the age of 48. Progressive restrictive lung disease developed during the last decade. Serological evaluation revealed IgM and IgA high titers against Coxiella burnetii. IgA, complement and amyloid deposits were detected in the walls of small arteries. Bronchial lavage and pleural effusions displayed numerous activated T lymphocytes. Analysis of endogenous lectins revealed alterations of the pulmonary defense system. The clinical history, histological and immunological findings suggest that chronic Q fever may induce remarkable changes in the immune system, comparable to autoimmune-reactive diseases.

Amyloidosis↗

PubMed1995

Expression of lectin, interleukin-2 and histopathologic blood group binding sites in prostate cancer and its correlation with integrated optical density and syntactic structure analysis.

The binding of several biotinylated biologic probes was determined in sections of 20 surgical specimens of prostate cancer and of 21 biopsy specimens of hyperplastic prostate. Whereas neither the immunomodulatory, galactoside-specific lectin from Viscum album nor the human beta-galactoside-specific lectin (M(r) 14 kd) or its specific antibody discerned any remarkable differences, the lectin from Urtica dioica (UDA) and interleukin-2, the in vitro production of which is enhanced by this lectin, exhibited obvious preference for hyperplastic cells. In addition, the presence of binding sites for chemically synthesized blood group determinants was tested. Carcinoma cases revealed a higher percentage of binding of synthetic blood group trisaccharide H than hyperplasia cases. Due to these differences, diverse parameters, derived from measurement of integrated optical density (IOD) and from syntactic structure analysis, were correlated with the extent of binding of these biologic probes for the tumor cases. Primarily, parameters that are related to computation of a minimum spanning tree were significantly different in positive and negative cases for both UDA and interleukin-2. For the binding of blood group trisaccharide H the 5C exceeding rate, the 2CV deviation index and the distance of neighboring tumor cells with an IOD > 5 were clearly dissimilar. Our results thus suggest an extension of the panel of biologic probes for prostate cancer and substantiate the usefulness of correlations of binding of selected biologic probes to features derived from the assessment of IOD and syntactic structure analysis.

Adenocarcinoma↗

PubMed1995

Glycoconjugate expression of chondrocytes and perichondrium during hyaline cartilage development in the rat.

Alterations in the expression of glycoconjugate structures during cartilage development in the chondrocranium, nasal skeleton, Meckel's cartilage, limb buds, vertebral bodies and ribs were investigated comparatively in 13 to 21-d-old rat embryos. The binding patterns of 24 biotinylated lectins were analysed in serial sections and compared with results obtained using histochemical methods. Proteoglycan distribution, assessed by conventional staining procedures, was not associated with lectin binding sites. During early fetal development, hyaluronate concentrations were enhanced in areas of prospective chondrogenesis. With few exceptions, the lectins showed a general increase in intensity of binding to mesenchymal structures. Con A (Canavalia ensiformis), DSL (Datura stramonium), and WGA (Triticum vulgare) displayed a ubiquitous distribution of binding sites. After incubation with LCA (Lens culinaris), PSA (Pisum sativum), STL (Solanum tuberosum), and VAA (Viscum album), characteristic differences in binding intensity between focal areas of developing mesenchyme were seen. DBA (Dolichus biflorus), ECL (Erythrina cristagalli), GSL I (Griffonia simplicifolia), LTA (Lotus tetragonobolus), SJA (Saphora japonica), UEA I (Ulex europaeus) and VVL (Vicia villosa) consistently failed to bind. During chondrogenesis a general reduction of lectin staining was detected. In early stages of development GSL II (Griffonia simplicifolia) was a specific marker of the prechondral blastema in the viscerocranium. PNA (Arachis hypogaea) selectively labelled the prevertebral blastema. In contrast, condensing mesenchyme of limb buds and viscerocranium was not stained. Using RCA (Ricinus communis), it was possible to distinguish chondroblasts from mature cells. All chondrocytes were stained by PSA, PHA-E, PHA-L (Phaseolus vulgaris E and L), and WGA, whereas Con A, LCA, and GSL II detected distinct differences between cartilage with different localisations. Cartilage matrix was constantly negative. Applying GSL II it was possible to distinguish specific segments of the perichondrium. From our results we conclude that especially high mannose oligosaccharides are amplified during development. Terminal sialic acid molecules, branched intralaminar glucose and/or mannose, respectively, internal galactose-(beta 1,4)-N-acetylglucosamine sequences as well as galactose-(beta 1,3)-N-acetylgalactosamine sequences in a preterminal position are diffusely distributed in mesenchymal tissue. In contrast, no evidence for the presence of terminal GlcNAc(beta 1,4)GlcNAc sequences and terminal alpha-fucosyl residues in (1,2) or (1,3)-linkage was obtained. Chondrogenesis appears to be correlated with a general reduction in the extent of expression of oligosaccharide structures. No proof of terminal N-acetylgalactosamine and alpha-galactose moieties was found, whereas our staining results document the expression of terminal beta-galactose structures in restricted areas of the developing mesenchyme.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetylglucosamine↗

PubMed1995

Lectin-binding sites in the epithelium of normal human appendix vermiformis and in acute appendicitis.

By using histochemical methods, the binding pattern of various lectins in the epithelium of normal human appendix vermiformis was assessed. In addition to plant and invertebrate sugar receptors with nominal monosaccharide specificity for alpha-L-Fuc (UEA-I), alpha-D-Man and alpha-D-Gluc (Con A), alpha-D-GalNAc (DBA), D-GalNAc (SBA, HPA) beta-D-Gal (RCA-I) and D-Gal (VAA), a mammalian beta-galactoside-specific lectin (MW, 14 kDa) was included in the applied panel. The apical surface of enterocytes presented binding sites for RCA-I on all cells, binding sites of UEA-I, DBA, SBA, HPA and VAA heterogeneously and no binding sites of Con A and 14 kDa. Binding sites of DBA, SBA, HPA, VAA and RCA-I within enterocytes were located primarily focally in a supranuclear position, whereas Con A and 14 kDa bound to the cytoplasm both in apical and basal cell parts. In the follicle-associated epithelium more enterocytes expressed SBA- and VAA-binding sites than in the crypt epithelium. No differences between the lectin-binding pattern of M-cells and enterocytes were found in the follicle-associated epithelium. Intraepithelial macrophages were heterogeneously positive for the full panel of applied lectins. In contrast, intraepithelial lymphatic cells expressed binding sites only for RCA-I and less prominently for Con A, VAA and 14 kDa. Goblet cell mucus contained lectin-binding sites in a heterogeneous manner: binding sites for Con A were not detected in goblet cells for DBA, SBA, VAA and 14 kDa in less than 20%, for UEA-I in 20-40%, for HPA in 40-60% and for RCA-I in 60-100% of the goblet cells. Secreted mucus differed in its lectin-binding capacity from intracellular goblet cell mucus selectively by an increase of UEA-I, SBA- and RCA-I-binding sites and a lack of 14 kDa-binding sites. Comparative study of lectin binding to goblet cell mucin in another region of the large intestine, namely the rectosigmoid, demonstrated that DBA, SBA and 14 kDa bound mainly to the distal colon, while UEA-I and VAA labelling was selectively found in appendiceal goblet cell mucin. Comparing the lectin-binding pattern in normal appendix epithelium and in appendicitis, the percentage of goblet cells expressing DBA- and SBA-binding sites in mucus globules was found to be about 4 times higher in appendicitis than in normal appendix.(ABSTRACT TRUNCATED AT 400 WORDS)

Acute Disease↗

PubMed1995

Affinity-purified antibodies against alpha-galactosyl residues from human serum: comparison of their binding in bovine testicular tissue with that of the Griffonia simplicifolia lectin (GSI-B4) and impact of labeling on epitope localization.

alpha-Galactosyl residues in the carbohydrate part of cellular glycoconjugates can serve as cell type-associated markers and are implicated in intercellular adhesion and biosignaling. This biological significance explains the interest to characterize probes with respective specificity as the Griffonia simplicifolia I-isolectin B4. Due to the documented occurrence of an alpha-galactoside-binding immunoglobulin G fraction in human serum we compared the extent of binding and its pattern for the lectin and the antibody using surface-immobilized extract proteins and fixed sections of bovine testicular tissue with known lectin reactivity. The antibody fractions were obtained either solely from affinity chromatography isolation on immobilized melibiose or after an additional step to deplete this fraction of galactoside-binding activities without pronounced specificity to the alpha-anomeric linkage. They yielded a rather indistinguishable reactivity in comparison to that of the lectin, when an indirect approach was used. Labeling of the antibodies with a hydrazide derivative of biotin did not affect the pattern of binding. However, significant differences were noted, when conjugation of label was targeted to amino groups via N-hydroxy-succinimide esters of biotin and digoxigenin despite performance of the modification under activity-preserving conditions. Notably, the apparent strong staining of Leydig cells and nuclei of primary spermatocytes, respectively, was not inhibitable by sugar. These differences were corroborated by a nonidentical response of the various probes in solid-phase assays with extract proteins. Thus, care should be exercised in the interpretation of histochemical data, obtained with this type of modified antibody. When these precautions are fulfilled, this immunoglobulin fraction from human serum has the potential as an alpha-galactosyl-specific histochemical tool.

Animals↗

PubMed1995

[Protein-carbohydrate recognition. Foundation and medical application with illustrations of tumor lectin studies].

Protein-carbohydrate interactions are involved in multifarious physiological processes. Together with antibodies and enzymes, lectins constitute the family of carbohydrate-binding proteins. The current research activities of tumor lectinology comprise the design of custom-made carrier-immobilized carbohydrate ligands (neoglycoconjugates), their application for the detection of specific binding sites and the evaluation of potential therapeutical approaches by blocking access or by directing drug conjugates to cell surface lectins, correlation of their expression to clinical parameters such as prognosis and their biochemical characterization. Thereby, mammalian lectins are made available to serve as tools. These experimental approaches are evaluated as regards their potential for improving cancer diagnosis and therapy.

Animals↗

PubMed1994

Expression of galactoside-specific endogenous lectins and their ligands in human oral squamous cell carcinoma.

Human endogenous lectins have a wide spectrum of biological functions. The present study analyses the expression of beta-galactoside specific and N-acetyl-D-galactosamine specific endogenous lectins in oral squamous cell carcinomas using biotinylated neoglycoproteins. The expression pattern of beta-galactosyl-containing glycoconjugates or ligands of beta-galactoside specific lectins in these tissues was also studied using an endogenous biotinylated lectin, the human 14-kDa lectin. For comparison a galactoside specific plant lectin from mistletoe, Viscum album was also employed. The results demonstrate that oral squamous cell carcinomas mainly express accessible binding sites for lactosylated neoglycoprotein (90%) while few carcinomas expressed mild amount of N-acetyl-D-galactosamine specific binding sites (40%). There was no difference in the binding patterns of these probes between well and less differentiated carcinomas. Expression of these neoglycoprotein binding sites were mostly concentrated in immature basaloid cells, indicating a possible association with cell proliferation. The binding pattern of D-galactosyl specific lectins (human 14-kDa and mistletoe lectins) showed conspicuous differences. This feature emphasizes the caution that needs to be exercised in interpreting the biological significance of results attained using plant lectins on human tissue.

Acetylgalactosamine↗

PubMed1994

Characterization of the macrophage migration inhibitory factor-binding site of sarcolectin and its relationship to human serum albumin.

The sialic acid-binding protein sarcolectin from human placenta specifically interacts with the lymphokine macrophage migration inhibitory factor, enabling its convenient purification and histochemical localization. After cyanogen bromide-mediated cleavage of sarcolectin one polypeptide with an apparent molecular weight of approximately 15,000 exhibited binding capacity to the labelled lymphokine, as revealed by ligand blotting. The N-terminal sequence stretch of this peptide is identical to the respective sequence of human serum albumin, following the internal methionine residue in position 298. Cleavage at a methionine moiety in position 446 can explain the size of the 15 KDa product of chemical degradation. Close similarity of circular dichroism of sarcolectin and human serum albumin added further evidence to their structural similarity, calling for further studies to rigorously define their relationship.

Amino Acid Sequence↗