Biomedical subjects

H J Gabius

Publications and source records attributed to H J Gabius.

350 records · Page 20Linked to original sources

PubMedDate not supplied

Endogenous sugar receptor (lectin) profiles of human retinoblastoma and retinoblast cell lines analyzed by cytological markers, affinity chromatography and neoglycoprotein-targeted photolysis.

Plant lectins have previously been employed to map the composition of cellular glycoconjugates on retinoblastoma and other tumor cells. To characterize the cellular receptors in protein-carbohydrate interactions, we have applied cytological markers (fluorescent neoglycoproteins) containing common carbohydrate building-blocks to investigate the presence of endogenous carbohydrate-binding proteins in six human retinoblastoma cell lines and one established human retinoblast cell line. The staining patterns showed similar expression of endogenous sugar receptors in all cell lines, with few qualitative differences. However, application of affinity chromatography using resins with immobilized carbohydrates as affinity ligands to isolate sugar receptors (lectins) with binding specificities for beta-D-galactosides, alpha-D-mannosides, alpha-L-fucosides alpha-D-glucosides and to N-acetyl-D-glucosamine and N-acetyl-D-galactosamine, respectively, revealed significant differences between the cell lines, emphasizing the value of complementary biochemical analysis. To demonstrate the practical use of this type of glycobiochemical profiling, selective photodestruction of retinoblastoma cells in vitro was accomplished following incubation with synthetic neoglycoprotein-hematoporphyrin conjugates and subsequent exposure to light. This phototherapeutical approach thus combined the inherent specificity of a neoglycoprotein for a particular cellular phenotype with targeted drug activation.

Carrier Proteins↗

PubMedDate not supplied

Vertebrate lectins and their possible role in fertilization, development and tumor biology (review).

Agglutination of cells is not only a functional test, employed in lectin characterization: the ability of lectins to mediate intercellular contacts may have physiological relevance beyond the test tube. Selected examples of advances in research on vertebrate lectins underscore their potential physiological significance in fertilization, development and in the pathogenesis of cancer.

Animals↗

PubMedDate not supplied

Endogenous tumor lectins: overview and perspectives.

Lectins are carbohydrate-binding proteins of non-immune origin that can be assayed as agglutinins. They are potential mediators in recognitive processes and cell adhesion by interaction with glycoconjugates. These functions are areas of particular relevance to tumor growth and metastatic spread. The presence of lectins in tumors has first been inferred by histochemical and cytological methods. The biochemical analysis for lectins with various specificities reveals differences in the lectin profile between tumors of different classes (eg, mammary adenocarcinoma, rhabdomyosarcoma, or teratoma) and of the same class (eg, testicular germ cell tumors) and differences in relation to normal tissues. The presence of endogenous lectins in tumors, their relation to lectins of normal tissues, and their interaction with glycoconjugates of tumors and normal tissues may contribute to an understanding of intercellular interactions during the complex process of metastatic spread, and may allow to establish a new tool for diagnosis and a lectin-based therapy.

Humans↗

PubMedDate not supplied

Characterization of membrane lectins in human colon carcinoma cells by flow cytofluorometry, drug targeting and affinity chromatography.

Flow cytofluorometry and drug targeting with labelled neoglycoproteins are used as tools to probe for membrane lectins in two human adenocarcinoma cell lines. Both cell lines express activities for galactosides, glucosides and fucosides. Affinity chromatography on gels with immobilized sugar leads to purification of an alpha-galactoside-binding protein at an apparent molecular weight of 64 kDa that also binds to lactose, maltose and fucose and exhibits Ca2+-requirement for binding, a beta-galactoside-binding protein without Ca2+-requirement at an apparent molecular weight of 14 kDa, and an alpha-glucosyl-binding protein without Ca2+-requirement at an apparent molecular weight of 34 kDa from both cell lines. The description of membrane lectins, documented here for the first human tumor cell lines, is an initial step towards a lectin-based improvement of the clinical management of human colon adenocarcinoma.

Adenocarcinoma↗

PubMedDate not supplied

Are matrix-immobilized neoglycoproteins, plant and human lectins and carbohydrate--binding antibodies from human serum mediators of adhesion in vitro for carcinoma and lymphosarcoma cells?

Mediation of cell adhesion by defined molecules can be studied by their immobilization onto a nitrocellulose matrix and incubation with cells. In order to infer the capacity of deliberately selected protein-carbohydrate interactions to establish sugar-inhibitable cell adhesion, a panel of immobilized neoglycoproteins was employed for the murine lymphosarcoma lines RAW-117 with low (P) and high (H10) metastatic capacity, a human mammary carcinoma line (DU4475) and three human colon carcinoma lines (C205, SW480, SW620). Exhibiting an otherwise rather similar behavior relative to the line with low metastatic potential, the murine line RAW117-H10 bound strongly to the matrix with carboxyl group-bearing N-acetylneuraminic acid and glucuronic acid as well as rhamnose. Whereas the analysis of carbohydrate-mediated adhesion yielded comparable results for the three colon carcinoma lines, a markedly reduced number of adherent cells was counted for matrix-attached alpha- and beta-galactosyl, alpha-mannosyl and alpha-glucosyl moieties in the case of the mammary carcinoma line, raising evidence for cell lineage-dependent alterations of this property. From the carbohydrate-binding proteins, the plant lectin, concanavalin A and Viscum album agglutinin almost invariably served well as cell adhesion molecules. Appropriate cell surface sugar receptors, probed with neoglycoproteins, and glycoconjugates, probed with lectins, thus can contribute to adhesion in this model system. The immobilized human beta-galactoside-binding lectin (Mr 14kDa) caused adhesion of the murine lines and one colon carcinoma line (SW480). Neither C-reactive protein under conditions that induce its activity as lectin nor serum amyloid P component nor a lactose-binding immunoglobulin G fraction from human serum were reactive. However, cell adhesion to the alpha-galactoside-binding immunoglobulin G fraction of human serum was seen with the murine line of low metastatic capacity and the mammary carcinoma line. Cells of this line adhered also to the mannan-binding protein from human serum, supporting the view for its potential role in host defence against aberrantly glycosylated tumor cells.

Adenocarcinoma↗

PubMedDate not supplied

Galactose-specific lectin from Viscum album as a mediator of aggregation and priming of human platelets.

Galactose-specific lectin from Viscum album (VAA) was found to induce aggregation of human platelets in a dose- and sugar-dependent manner. Small nonaggregating concentrations of VAA primed the response of platelets to known aggregants (ADP, arachidonic acid, thrombin, ristocetin, and A23187). VAA-induced platelet aggregation was completely reversible by addition of the sugar inhibitor lactose and the platelets from disrupted aggregates maintained the response to other aggregants. The lectin-induced aggregation of washed platelets was more resistant to metabolic inhibitors than thrombin- or arachidonic acid-dependent cell interaction. In contrast to the related galactose-specific lectin from Ricinus communis and the soy bean agglutinin, the lectin did not aggregate liposomes prepared from total platelet lipids, indicating different affinities of aggregation-mediating lectins to platelet glycolipids.

Arachidonic Acid↗

PubMedDate not supplied

Modulation of lectin-triggered superoxide release from neutrophils of tumor patients with and without chemotherapy.

Superoxide production by neutrophils is believed to contribute to the efficiency of the host defence system. This activity is stimulated by the mannose-specific lectin concanavalin A, the N-acetylglucosamine/neuraminic acid-specific wheat germ agglutinin and the galactoside-specific lectins from Viscum album and human placenta. To assess whether this aspect of immune function is affected in cancer patients without or with treatment, neutrophil preparations from 69 patients were examined. Reductions in O2.(-)-production were observed for bronchial carcinoma patients after incubation with concanavalin A and the human lectin, while samples from breast cancer patients without or with treatment exhibited no significantly altered activity in the presence of each of the four agglutinins. Chemotherapy of lung and colorectal carcinoma patients reduced the neutrophilic response to concanavalin A and Viscum album agglutinin. As similarly shown for 9 specimens from other carcinoma types and from hemopoietic malignancies, there is no general impairment of responsiveness. In addition to the property of the lectin, the large extent of interindividual variation should be taken into account when it is attempted to enhance this factor of the host defence system against infections and malignant cells.

ABO Blood-Group System↗

PubMedDate not supplied

Effects of castration and thyroidectomy on expression of lectin-binding sugar moieties and endolectins in mouse submandibular glands. A glycohistochemical study.

The aims of this study were to assess histochemically by means of biotinylated lectins and neoglycoproteins the effects of castration and thyroidectomy on the expression of carbohydrate moieties and endogenous sugar-binding proteins (endolectins), respectively, in submandibular glands of mice. Characteristic binding patterns depending upon the type of lectin were observed primarily in the granular convoluted tubules. For the first time carbohydrate-binding sites were also localized in this glandular tissue. Moreover, the endocrine status was found to affect the histochemical expression of sugar moieties of glycoconjugates as well as endolectins, thus modifying both sides of presumed protein-carbohydrate interactions. Further work is needed to identify these molecules and to understand better their endogenous roles.

Animals↗