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Query: KEGG:D02003 (NBT)
 1,323 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cell dissociation and acquisition of cell motility are major events in morphogenesis, wound repair, and cancer invasion and metastasis. We have used the NBT-II bladder carcinoma cell line as a model system to study the mechanisms of these events. Upon exposure to acidic fibroblast growth factor (aFGF), NBT-II cells undergo morphological changes that resemble those described in epithelial-mesenchymal transitions, i.e., dissociation of some or all polygonal epithelial cells and their transformation into motile, fibroblastic-like cells. The disruption of intercellular contacts, which accompanies cell dissociation and acquisition of motility, is correlated with a redistribution of E-cadherin, a Ca(2+)-dependent cell adhesion molecule, over the entire cell surface and within the cytoplasm. However, these modifications are not accompanied by a reduction of the intercellular adhesiveness or a loss of E-cadherin expression. Moreover, the formation of intercellular contacts between fibroblastic-like NBT-II cells results in the relocation of epithelial cadherin (E-cadherin) immunoreactivity on lateral membranes, but is not sufficient to abrogate cell motility. Finally, the overexpression of E-cadherin by NBT-II cells stably transfected with a plasmid containing the mouse E-cadherin cDNA does not impair the scattering effect of aFGF, indicating that high levels of E-cadherin expression do not prevent cells from disrupting their intercellular connections. Altogether, these results suggest that the scattering activity of aFGF is not mediated by direct modulations of E-cadherin expression.
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PMID:E-cadherin expression during the acidic FGF-induced dispersion of a rat bladder carcinoma cell line. 137 93

During metastatic spread, locomotion mediated by extracellular matrix components of basement membranes and connective tissues has been invoked as a prerequisite to invasion. We studied the interactions of the rat bladder carcinoma cell line NBT-II with fibronectin, laminin, and collagens (types I, III, IV, and V). They all promoted cell attachment and spreading. To analyze their scatter potential, we studied epithelial outgrowth and/or peripheral cell dispersion from tumor aggregates. All matrix components allowed partial collapse of the aggregate and the appearance of a cellular monolayer forming a halo around the aggregate. No peripheral cell dispersion occurred on fibronectin and laminin. Collagens (especially types I and III) promoted the dispersion of peripheral NBT-II cells with various speeds of locomotion, as revealed by time-lapse videomicroscopy. With the exception of cells at the periphery on collagens, cells inside the halo did not exchange neighbors, migrated transiently as an epithelial sheet during halo formation, and finally remained stationary. These effects were reproduced with NBT-II tumor fragments obtained from nude mice. Tumor cells were linked together with desmosomes (as revealed by immunoreactivity against desmoglein). Migration on collagens correlated with the mechanical disruption of intercellular contacts and consequently with the progressive disappearance of desmoglein immunoreactivity. Immunofluorescence studies also revealed a reduced expression of the epithelium-specific cell adhesion molecule liver cell adhesion molecule after contact with collagens. These results suggest that direct interactions with collagens may favor single cell infiltration by bladder carcinoma.
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PMID:Collagen-mediated dispersion of NBT-II rat bladder carcinoma cells. 229 46

C-CAM is a Ca(2+)-independent cell adhesion molecule (CAM) that mediates intercellular adhesion of isolated rat hepatocytes. It is widely distributed in epithelia, where its presence both at lateral cell borders and on apical cell surfaces suggests that it may have diverse biological functions. Two major isoforms, C-CAM1 and C-CAM2, which differ in the lengths of their cytoplasmic domains, have been identified. The lack of suitable in vitro systems has so far prevented a detailed study of the physiological role of C-CAM in epithelia. We now report on the identification, biochemical characterization and functional analysis of C-CAM isoforms in the established epithelial cell line NBT II, derived from a chemically induced carcinoma of rat bladder. C-CAM in NBT II cells is a 110-115 kDa cell surface glycoprotein located predominantly at sites of cell-cell contact but also present on the apical cell surface. Northern blotting analysis revealed the presence of both C-CAM1 and C-CAM2, with the major transcripts for both isoforms present within the 4.0 kb size range. The dissociation of NBT II cell colonies by anti-C-CAM antibodies indicated that at least one function of C-CAM in these cells is to mediate intercellular adhesion. The maintenance of extensive cell-cell contacts and the expression of C-CAM at the contact sites in cells grown in low Ca2+ medium suggested that, like its counterpart in hepatocytes, C-CAM in NBT II cells may be a Ca(2+)-independent cell-cell adhesion molecule. The co-localization and coordinate reorganization of both C-CAM and actin by anti-C-CAM antibodies indicated that these two proteins were associated and suggested that interactions with the cytoskeleton may be important for the regulation of C-CAM function. The specific upregulation of C-CAM1 in cells induced to undergo epithelial to mesenchymal-like transitions (EMT) by the serum substitute Ultroser G suggested that C-CAM isoforms are important modulators of the adhesive properties of these cells.
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PMID:Differential regulation of C-CAM isoforms in epithelial cells. 792 30

The homophilic cell adhesion molecule CEACAM1 (C-CAM, BGP, CD66a) occurs as two coexpressed isoforms, CEACAM1-L and CEACAM1-S, in epithelia, endothelia, and leukocytes. CEACAM1-L can inhibit tumor growth; this effect is influenced by CEACAM1-S. To characterize the growth regulatory properties of CEACAM1, we analyzed the expression patterns of the isoforms, and here we demonstrate that both the expression levels and the S:L isoform ratios differ in proliferating and quiescent rat epithelial cells. Quiescent prostate NbE cells expressed more CEACAM1 than quiescent bladder NBT-II cells, a pattern that correlated with the expression levels in the parental tissues. In contrast, both the expression levels and the isoform ratios were strikingly similar in proliferating NbE and NBT-II cells, showing that a particular CEACAM1 expression pattern is compatible with cell proliferation. However, in confluent cells, CEACAM1 seemed to exert inhibitory effects on cell proliferation. Addition of anti-CEACAM1 antibodies to quiescent, confluent cells caused decreased expression of the cyclin-dependent kinase inhibitor, p27Klp1, stimulated growth factor-dependent DNA synthesis, and altered the S:L isoform ratio toward the ratio characteristic of proliferating cells. Taken together, our data suggest that CEACAM1 contributes to contact inhibition of cell proliferation in confluent cells but allows proliferation when expressed at different isoform ratios.
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PMID:The tumor growth-inhibiting cell adhesion molecule CEACAM1 (C-CAM) is differently expressed in proliferating and quiescent epithelial cells and regulates cell proliferation. 1072 82

Growth factor receptors, extracellular matrix receptors, and cell-cell adhesion molecules co-operate in regulating the activities of intracellular signaling pathways. Here, we demonstrate that the cell adhesion molecule CEACAM1 co-regulates growth-factor-induced DNA synthesis in NBT-II epithelial cells in a cell-density-dependent manner. CEACAM1 exerted its effects by regulating the activity of the Erk 1/2 MAP kinase pathway and the expression levels of the cyclin-dependent kinase inhibitor p27(Kip1). Interestingly, both inhibitory and stimulatory effects were observed. Confluent cells continuously exposed to fetal calf serum showed little Erk activity and DNA synthesis compared with sparse cells. Under these conditions, anti-CEACAM1 antibodies strongly stimulated Erk activation, decreased p27 expression, and induced DNA synthesis. In serum-starved confluent cells, re-addition of 10% fetal calf serum activated the Erk pathway, decreased p27 expression, and stimulated DNA synthesis to the same levels as in sparse cells. Under these conditions anti-CEACAM1 antibodies de-activated Erk, restored the level of p27, and inhibited DNA synthesis. These data indicate that CEACAM1 mediates contact inhibition of proliferation in cells that are constantly exposed to growth factors, but co-activates growth-factor-induced proliferation in cells that have been starved for growth factors; exposure to extracellular CEACAM1 ligands reverts these responses.
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PMID:Control of density-dependent, cell state-specific signal transduction by the cell adhesion molecule CEACAM1, and its influence on cell cycle regulation. 1595 Jun 23