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J Behrens

Publications and source records attributed to J Behrens.

66 records · Page 4Linked to original sources
PubMed1991

Dominant and recessive genes involved in tumor cell invasion.

The past year has been the discovery and further analysis of several genes and protein products that are critically involved in the generation of invasive and metastatic tumor cells. Like oncogenes and tumor suppressor genes, the genes responsible for invasive and metastatic phenotypes can function in a dominant or recessive fashion. In this review, particular emphasis will be given to the dominantly acting genes encoding the cell adhesion molecule CD44 and the motility factor scatter factor, and the recessively acting genes encoding the cell adhesion molecule E-cadherin and nm23.

Amino Acid Sequence↗
PubMed1991

E-cadherin-mediated cell-cell adhesion prevents invasiveness of human carcinoma cells.

The ability of carcinomas to invade and to metastasize largely depends on the degree of epithelial differentiation within the tumors, i.e., poorly differentiated being more invasive than well-differentiated carcinomas. Here we confirmed this correlation by examining various human cell lines derived from bladder, breast, lung, and pancreas carcinomas. We found that carcinoma cell lines with an epithelioid phenotype were noninvasive and expressed the epithelium-specific cell-cell adhesion molecule E-cadherin (also known as Arc-1, uvomorulin, and cell-CAM 120/80), as visualized by immunofluorescence microscopy and by Western and Northern blotting, whereas carcinoma cell lines with a fibroblastoid phenotype were invasive and had lost E-cadherin expression. Invasiveness of these latter cells could be prevented by transfection with E-cadherin cDNA and was again induced by treatment of the transfected cells with anti-E-cadherin mAbs. These findings indicate that the selective loss of E-cadherin expression can generate dedifferentiation and invasiveness of human carcinoma cells, and they suggest further that E-cadherin acts as an invasion suppressor.

Antibodies, Monoclonal↗
PubMed1990

Scatter factor: molecular characteristics and effect on the invasiveness of epithelial cells.

The generation of invasiveness in transformed cells represents an essential step of tumor progression. We have previously shown that MDCK epithelial cells, which are deprived of intracellular adhesion by the addition of anti-Arc-1/uvomorulin antibodies, become invasive for collagen gels and embryonal heart tissue (Behrens, J., M. M. Mareel, F. M. Van Roy, and W. Birchmeier. 1989. J. Cell Biol. 108: 2435-2447.). Here we examined whether invasiveness is also induced by scatter factor, which is known to dissociate epithelial cells (Stoker, M., E. Gherardi, M. Perryman, and J. Gray. 1987. Nature (Lond.). 327:239-242.). Scatter factor was purified to homogeneity from conditioned medium of human fibroblasts by heparin-Sepharose chromatography, followed by cation exchange chromatography, gel filtration, or preparative SDS gel electrophoresis. We found that scatter factor represents a 92,000 mol wt glycoprotein which, apparently, is converted by limited proteolysis into disulfide-linked 62,000 and 34/32,000 mol wt subunits. Reversed phase HPLC and sequence analysis of tryptic peptides confirmed the suggested molecular structure, and revealed further that scatter factor exhibits sequence similarities to hepatocyte growth factor and to plasminogen. Purified scatter factor in fact induces the invasiveness into collagen matrices of MDCK epithelial cells, and induces or promotes the invasiveness of a number of human carcinoma cell lines. Apparently, the effect on the human cells depends on their respective degree of differentiation, i.e., cell lines with a less pronounced epithelial phenotype were more susceptible to the factor. Scatter factor does not seem to influence synthesis, steady-state level, and phosphorylation of the cell adhesion molecule Arc-1/uvomorulin. Thus, scatter factor represents a clearly defined molecular species which induces, in vitro, the progression of epithelial cells to a more motile, i.e., invasive phenotype.

Amino Acid Sequence↗
PubMed1989

Dissecting tumor cell invasion: epithelial cells acquire invasive properties after the loss of uvomorulin-mediated cell-cell adhesion.

The generation of invasiveness in transformed cells represents an essential step of tumor progression. We show here, first, that nontransformed Madin-Darby canine kidney (MDCK) epithelial cells acquire invasive properties when intercellular adhesion is specifically inhibited by the addition of antibodies against the cell adhesion molecule uvomorulin; the separated cells then invade collagen gels and embryonal heart tissue. Second, MDCK cells transformed with Harvey and Moloney sarcoma viruses are constitutively invasive, and they were found not to express uvomorulin at their cell surface. These data suggest that the loss of adhesive function of uvomorulin (which is identical to E-cadherin and homologous to L-CAM) is a critical step in the promotion of epithelial cells to a more malignant, i.e., invasive, phenotype. Similar modulation of intercellular adhesion might also occur during invasion of carcinoma cells in vivo.

Antibodies, Monoclonal↗
PubMed1987

Inhibitory action of transforming growth factor beta on endothelial cells.

In the present study, we show that transforming growth factor beta (TGF-beta) strongly inhibits fibroblast growth factor-induced proliferation and motility of bovine endothelial cells in tissue culture. TGF-beta also prevents the phorbol ester-induced invasion of capillary endothelial cells into collagen matrices--i.e., blocks angiogenesis in vitro. TGF-beta promotes the incorporation of fibronectin into the extracellular matrix of endothelial cells and stimulates the secretion of other proteins--mainly of 55- and 180-kDa components. We show furthermore that endothelial cells express TGF-beta receptors similar in size to those of other tissue culture cell lines: a 280-kDa complex is present in subconfluent cells, and 85- and 72-kDa protein bands are seen in confluent cells. The various effects of TGF-beta on endothelial cells suggest that these cells are an important target of TGF-beta during wound healing and angiogenesis.

Animals↗
PubMed1985

Dissociation of Madin-Darby canine kidney epithelial cells by the monoclonal antibody anti-arc-1: mechanistic aspects and identification of the antigen as a component related to uvomorulin.

It has previously been shown that the monoclonal antibody anti-Arc-1 dissociates Madin-Darby canine kidney (MDCK) epithelial cells and changes their morphology in vitro (Imhof, B.A., H.P. Vollmers, S.L. Goodman, and W. Birchmeier, 1983, Cell, 35:667-675). In this article we demonstrate that the anti-Arc-1 antibody recognizes an uvomorulin-like molecule on MDCK cells, i.e., it immunoprecipitates an 84-kD protein fragment from a tryptic digest of cell surfaces in the presence of Ca2+ (as does anti-uvomorulin antiserum). Furthermore, anti-uvomorulin antiserum prevents the binding of anti-Arc-1 to MDCK cells. The distribution of the Arc-1 antigen is also quite similar to that of uvomorulin: it is enriched at the cell-cell contacts both of MDCK cells and of cells in various canine tissues. In the intestinal epithelium the antigen could be further localized in the region of the junctional complex. To study the mechanism of action of the dissociating antibody, MDCK cells grown on Nuclepore filters in Boyden chambers were exposed to anti-Arc-1 from either the upper or lower compartment. It could be shown that the antibody interfered with cell adhesion only from the basolateral but not from the apical cell surface. Antibody action was inhibited in the presence of colchicine but not cytochalasin B. Furthermore, cell dissociation was prevented when the cellular cAMP level was raised. These findings indicate that the anti-Arc-1 antibody acts on a target below the tight junctions (possibly on the antigen located in the junctional complex), and they confirm that cytoskeleton and metabolic factors are actively involved in the maintenance of junctional integrity.

Animals↗
PubMed1978

Uterotropic activity of cis and trans isomers of zearalenone and zearalenol.

The cis and trans isomers of zearalenone [2,4-dihyroxy-6-(10-hydroxy-6-oxo-1-undecenyl)-benzoic acid mu-lactone] and zearalenol [2,4-dihydroxy-6-(6,10-dihydroxy-1-undecenyl)-benzoic acid mu-lactone] were tested for uterotropic activity in the white rat. The metabolites were administered through the oral route (per os) and by topical application to the freshly shaven skin on the back. cis-Zearalenone was significantly more active than trans when fed orally to the rats in the diet or when applied topically by skin application. However, the cis isomer of zearalenol was not significantly different than its trans isomer. trans-Zearalenone was less active than trans-zearalenol.

Animals↗
PubMed1976

Substances interfering with the gas-liquid chromatographic determination of T-2 mycotoxin.

Two substances interfering with the gas-liquid chromatographic (GLC) detection of T-2 mycotoxin were identified as 1-glyceryl-monooleate and 1-glycerylmonolinoleate. These monoglycerides are natural products formed by species of Fusarium growing on cereal grains and are also additives contained in liquid vegetable and animal fats added to the feed mixture. The monoglycerides can be removed from the analytical sample by resolution by thin layer chromatography prior to separation by GLC. Trimethylsilyl ether derivatives of the monoglycerides and T-2 toxin have almost identical retention times on 3% OV-1 columns, whereas the trifluoroacetyl and pentafluoropropionyl derivatives give baseline separation on the same column. The monoglycerides can be misidentified as the T-2 toxin in analyses involbing GLC.

Chromatography, Gas↗
PubMedDate not supplied

Biomolecular markers of malignancy in human uveal melanoma: the role of the cadherin-catenin complex and gene expression profiling.

In recent years there has been a trend towards conservative management of uveal melanoma (UM), aimed at preserving the eye and vision. Despite improvements with this approach, recurrent tumour and metastatic disease still occur, and the management remains problematic. As a result of these limitations, there is interest in gaining a greater understanding of molecular changes associated with aggressive disease patterns in UM. This might result in new, more effective and less toxic therapies as well as provide prognostic information for defining subgroups of patients with a less favourable prognosis as potential candidates for adjuvant therapies. Accumulating evidence over the past decade suggests that disturbance in the cadherin-catenin adhesion complex is critical in the process leading to invasion and metastasis of many cancers. The recent advent of DNA micro-array technology now offers an unprecedented ability to study these molecules and others associated with malignant transformation. In this mini-review, the aspects of tumour progression in which cadherin-catenin may be involved are dealt with along with the potential application of DNA micro-array technology to the problem in UM.

Biomarkers, Tumor↗
PubMedDate not supplied

Cell contacts, differentiation, and invasiveness of epithelial cells.

Histotypic differentiation and prognosis of carcinomas are intimately linked phemonena, i.e. poorly differentiated tumors show increased invasiveness and have a worse prognosis compared to well-differentiated tumors. In poorly differentiated carcinomas, loss of epithelial cell contacts is frequently observed; this allows the cells to break away from the primary tumor and invade surrounding tissue. The molecular basis for the disturbance of epithelial junction formation in tumors has been the subject of recent research. It has become clear that the epithelial cell adhesion molecule E-cadherin and its associated proteins, the catenins, are of central importance for the establishment of the epithelial phenotype and the prevention of invasiveness, and that aberrations in these components contribute to metastasis. The molecular mechanisms controlling the E-cadherin-based adhesion system in normal epithelial cells and in invasive carcinomas are the topic of this review.

Animals↗
PubMedDate not supplied

Expression of E-cadherin and catenins in invasive mammary carcinomas.

E-Cadherin has been shown to be an invasion tumor suppressor gene, but few epidemiological studies have revealed relationships between loss of E-cadherin expression and invasive tumor growth and/or metastasis. The adhesive function of E-cadherin is dependent on the integrity of the catenin components which link E-cadherin to the actin filaments. In order to achieve a better correlation between the loss of cell adhesion and metastasis in cancer, we decided to investigate both E-cadherin and the catenins. 157 archival primary mammary carcinomas were immunohistochemically studied using antibodies against E-cadherin, alpha-, beta- and gamma-catenin. The following results were obtained: (a) Independent of the presence of E-cadherin, loss of expression of one or multiple catenins was noted; (b) loss of E-cadherin and alpha-catenin expression was more pronounced in lobular-type than ductal-type carcinomas; c) axillary lymph node metastases were completely lacking only in the group where expression of E-cadherin, alpha- and beta- catenin was preserved: d) no correlation between expression of c-erbB-2 and E-cadherin or one of the catenins was found. The results demonstrate for the first time that consideration of both the expression of E-cadherin and of the three catenins is useful in evaluation of the metastatic potential of mammary carcinomas.

Axilla↗