Biomedical subjects

F Herzberg

Publications and source records attributed to F Herzberg.

15 recordsLinked to original sources

PubMed1996

IL-4 and TNF-alpha induce changes in integrin expression and adhesive properties and decrease the lung-colonizing potential of HT-29 colon carcinoma cells.

The colon carcinoma cell line HT-29 was used to explore the potential of interleukin-4 (IL-4) and tumor necrosis factor alpha (TNF-alpha) to modify integrin expression and adhesive functions of tumor cells in vitro and to examine corresponding metastatic effects in vivo. Preincubation of HT-29 cells with 100 U/ml of IL-4 for 48 h downregulated the surface expression of the integrin subunits alpha 2, alpha 3, beta 1 and beta 4 after 48 h, whereas the alpha 1 subunit was upregulated. In contrast, 100 U/ml to TNF-alpha selectively upmodulated the expression of alpha v. Attachment to fibronectin of cells treated with IL-4 increased twofold (63.5% vs 32.4%). Adhesion to fibronectin (54.0% vs 32.4%) and vitronectin (37.9% vs 16.4%) was elevated in the case of TNF-alpha stimulation. Using an experimental metastasis model, HT-29 cells showed a significant reduction of their lung-colonizing potential in nude mice when preincubated with IL-4 for 48 h before intravenous injection. The decrease also observed for TNF-alpha-treated cells was less pronounced. The data indicate that the cytokines IL-4 and TNF-alpha can act as direct regulators of adhesive mechanisms of tumor cells bearing adequate receptors, thus influencing lung-colony formation.

Animals↗

PubMed1995

Properties of the carcinoma-associated antigen MH 99/KS 1/4 in normal and transformed human keratinocytes: regulation of synthesis, molecular cross-linking and ultrastructural localization.

A 38-kDa cell-surface glycoprotein defined by monoclonal antibody MH 99 is markedly increased in many epithelial tumours. In normal human skin, it is a characteristic marker for germ-cell phenotypic tissues. Although the gene encoding the MH 99 antigen has recently been cloned, and several histological and biochemical studies have been performed, the biological function of this interesting antigen still remains unknown. In the present study, we examined the synthesis of MH 99 in keratinocyte populations showing different in vitro differentiation capacity. Normal keratinocytes, spontaneously immortalized keratinocytes (cell line HaCaT), three SV-40-transformed keratinocyte lines (130, 425, and HaSV), and two squamous cell carcinoma lines (SCL-1 and SCL-2), were compared. Radioimmunoprecipitation revealed the highest levels of synthesis in cell populations with the least differentiation. This was paralleled by an increase of MH 99 synthesis in normal keratinocytes cultured in low concentrations of Ca2+ and by an increase of MH 99 synthesis during subculture of normal keratinocytes. Both phenomena were paralleled by an opposite behaviour of a differentiation marker. Molecular cross-linking and subsequent immunoprecipitation led to a decrease of the MH 99 signal, but an increase of a high molecular weight protein signal was seen. After cleavage of the crosslinker, the MH 99 signal reappeared, whereas the signal of the large protein remained unchanged. Thus, the MH 99 antigen may be associated with a high molecular weight protein on the cell surface, supporting the suggestion of a receptor-like function. Phosphorylation of the molecule could not be detected. Immunoelectron microscopy revealed homogeneous distribution on the cell surface, but cells of the same culture exhibited clear differences in their MH 99 expression. A concept for MH 99 regulation in normal and transformed human keratinocyte populations in vitro is proposed, showing that the synthesis of MH 99 is inversely correlated with cell differentiation. The association with a high molecular weight protein supports the suggestion that the MH 99 antigen interacts with other molecules.

Antibodies, Monoclonal↗

PubMed1991

Expression of XBcad, a novel cadherin, during oogenesis and early development of Xenopus.

A gastrula cDNA library was screened using a cDNA probe encoding the cytoplasmic domain of uvomorulin, a mouse Ca(2+)-dependent cell adhesion molecule. A Xenopus cDNA clone was isolated, which shares an amino acid sequence identity with uvomorulin of 91% in the transmembrane and 89% in the cytoplasmic domain. A restriction fragment of 397 bp representing the lowest degree of identity to all other known cadherin sequences was used to study the expression pattern of this Xenopus cadherin gene on RNA and protein level. The 397 bp restriction fragment was expressed bacterially as fusion protein, against which polyclonal antibodies were raised. An mRNA of 3.9 kb and a corresponding 125 kDa glycoprotein could be identified. Both molecules are present throughout oogenesis and early embryogenesis. When cleavage starts, the protein becomes integrated into the newly formed membranes. This polypeptide is found at cell membranes of all blastomeres except those at the outer surface of the embryo. Immunoblots and immunohistological analyses of adult organs reveal that this protein is expressed in pituitary gland, lung and kidney. It could not be detected in liver, heart and skeletal muscle. Since this cadherin differs in its tissue distribution from that of U-cadherin and in sequence alignments from ep-cadherin, it was termed XBcad for Xenopus blastomere cadherin.

Amino Acid Sequence↗

PubMed1990

Identification of Ca2(+)-dependent cell adhesion molecules in Xenopus by the use of interspecies homology.

Ca2(+)-dependent cell adhesion molecules (CAMs) are transmembrane glycoproteins structurally and functionally related in mammalian and avian species. This suggests that Ca2(+)-dependent CAMs consist of an evolutionary conserved gene family. Antibodies or cDNA probes specific either to the extracellular part or the cytoplasmic domain of uvomorulin were compared for their ability to detect corresponding molecules in Xenopus. Only antibodies directed against the evolutionary highly conserved cytoplasmic domain afforded a clear membrane staining on sections of Xenopus embryos or on cultured Xenopus epithelial cells. However, these antibodies recognized different polypeptides of 156, 140 and 128 kDa in immunoblots prepared from cell lysates of epithelial, neural, muscle and embryonic tissues. In concordance with the antibody analysis, signals in Northern hybridizations were only obtained when the cDNA probe encoding the cytoplasmic domain of uvomorulin was used. Here again, this cDNA probe revealed different mRNA species of 4.3, 4.1, 3.8 and 3.2 kb in the studied cell types. These results provide further direct evidence that the Ca2(+)-dependent CAMs are evolutionary conserved. The variety of polypeptides and transcripts observed in Xenopus indicates that several members of this gene family were detected by the use of probes specific to conserved sequences. More important, with this approach we also identified members of this gene family in the early stages of Xenopus development. Since these proteins were present in mature eggs but not in oocytes, we assume a maternal store of Ca2(+)-dependent CAM RNAs whose translation might be initiated during egg maturation.

Animals↗

PubMed1986

Morphological changes in Trypanosoma congolense after proteolytic removal of the surface coat.

Bloodstream forms of Trypanosoma congolense were exposed to proteases at various concentrations, and the consequences of this treatment were continuously examined by electron microscopy. Unexpectedly, proteolysis did not simply result in the removal of the surface coat, but in dramatic morphological changes characterized by membrane adhesions, subsequently leading to flagella/plasmamembrane and to plasmamembrane/plasmamembrane fusions. The resulting axonemal internalization and rearrangement of cell organelles were followed by profound changes in cell shape. The axonemal motility, however, was maintained.

Animals↗

PubMed1974