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

Since one crucial step in tumor progression consists of the acquisition of invasive and metastatic properties, it is important to analyze the mechanisms used by cancer cells to disperse. Among the possible mechanisms of cell dispersion, cell motility appears as a central phenomenon that still needs to be understood at the molecular level. Our experimental approach to the contribution of cell motility in carcinoma cell dissemination is based on the study of the NBT-II rat bladder carcinoma cell line. The epithelial cell line gives rise to isolated, actively migrating, fibroblast-like cells in response to specific stimuli (collagens and acidic fibroblast growth factor [aFGF]). Analysis of the scattering response indicates that the different stimuli can synergize, leading to increased motility and invasiveness. NBT-II cells have two types of response to aFGF: they can either proliferate or scatter. In addition, the two responses are mutually exclusive, suggesting that the cell status can dictate whether or not tumor cells will disperse after exposure to a scatter factor. Finally, recent studies on the involvement of epithelial-specific cadherins in the process of aFGF-induced cell scattering indicate that a sustained expression of E-cadherin is not sufficient to protect cells from dispersing. In conclusion, our experimental model offers the opportunity to dissect the molecular events leading to tumor cell dissemination.
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PMID:Involvement of cell motility in tumor progression. 751 90

Tumor progression involves the emergence of cell variants with increased proliferative and invasive potentialities. The acquisition of the invasive and metastatic behavior is associated with modulation of cell-cell and cell-substrate interactions. Tumor cells have to dissociate from the primary tumor and migrate through the basal lamina and the surrounding stroma before reaching the vessels. An aberrant expression of some growth factors and their cognate receptors, may contribute to an increase malignancy of tumor cells. We have postulated than such growth factors could be involved in the early events of metastatic spreading by altering cell interactions within a tumor, including proliferation, scattering and migration of tumor cells. In the rat bladder carcinoma NBT-II cell experimental model, we have shown that FGF-1 is a multifunctional factor during tumor progression; FGF-1 acts as a mitogenic factor, a scatter factor, an angiogenic factor, an inducer of matrix degradating enzymes and a tumorigenic factor. NBT-II cells producing constitutively FGF-1 are more invasive, tumorigenic and metastatic than non-producing cells. However, we have shown that within a tumor, FGF-1 producing cells are not dominant in vivo but rather confer by a community effect an "en bloc" behavior to the whole cell collective. This effect could be established either directly by a paracrine mechanism or indirectly by other induced factors. We provide evidence for a novel concept in tumor biology: tumor progression may result from a community effect mediated by a growth/scatter factor produced by a minority of the carcinoma cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Molecular aspects of invasiveness and metastasis]. 754 9

The rat bladder carcinoma epithelial NBT-II cell line undergoes, in vitro, a morphological transition to a fibroblast-like state in the presence of different growth factors. We have selected, in vivo, a metastatic clone, designated M-NBT-II, which has a mesenchymal phenotype and secretes into the culture medium a factor able to dissociate epithelial clusters of NBT-II or MDCK cells. This factor was designated scatter factor-like (SFL) by analogy to the HGF/SF, which has the same dissociating effect in these two cell lines. Here, we show that SFL factor and HGF/SF are different factors: (i) no HGF/SF transcripts could be detected using either specific rat HGF/SF cDNA probes or PCR; (ii) blocking antibodies against rat HGF/SF do not inhibit the SFL activity; and (iii) crude culture medium or partially purified SFL factor-containing fractions do not induce MDCK tubulogenesis, a biological assay that is specific for HGF/SF activity in vitro. We report the partial purification of the SFL factor, based on ion exchange and reverse-phase chromatography. The results indicate that the M-NBT-II metastatic variant secretes a dissociating factor sharing some common biological properties with the HGF/SF, which suggests that the SFL factor is a member of the HGF/SF family and may be involved in tumor progression.
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PMID:A scatter factor-like factor is produced by a metastatic variant of a rat bladder carcinoma cell line. 792 34

Epithelial-mesenchymal transition (EMT) is an essential morphogenetic process during embryonic development. It can be induced in vitro by hepatocyte growth factor/scatter factor (HGF/SF), or by FGF-1 in our NBT-II cell model for EMT. We tested for a central role in EMT of a zinc-finger protein called Slug. Slug mRNA and protein levels were increased transiently in FGF-1-treated NBT-II cells. Transient or stable transfection of Slug cDNA in NBT-II cells resulted in a striking disappearance of the desmosomal markers desmoplakin and desmoglein from cell-cell contact areas, mimicking the initial steps of FGF-1 or HGF/SF- induced EMT. Stable transfectant cells expressed Slug protein and were less epithelial, with increased cell spreading and cell-cell separation in subconfluent cultures. Interestingly, NBT-II cells transfected with antisense Slug cDNA were able to resist EMT induction by FGF-1 or even HGF/SF. This antisense effect was suppressed by retransfection with Slug sense cDNA. Our results indicate that Slug induces the first phase of growth factor-induced EMT, including desmosome dissociation, cell spreading, and initiation of cell separation. Moreover, the antisense inhibition experiments suggest that Slug is also necessary for EMT.
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PMID:The zinc-finger protein slug causes desmosome dissociation, an initial and necessary step for growth factor-induced epithelial-mesenchymal transition. 918 71

Various mechanisms of epithelial cell plasticity in morphogenesis have been studied at the genetic and molecular levels. Several control genes have been identified including genes encoding transcription factors and growth factor receptors. These mechanisms may be reactivated during the progression of carcinomas. One of the mechanisms underlying epithelial plasticity is the epithelial-mesenchymal transition. This process has been extensively studied using the NBT-II bladder carcinoma cell line. Cells of this line undergo a reversible transition following exposure to several growth factors including FGF-1, EGF, TGFalpha and SF/HGF, which activate tyrosine kinase surface receptors. Two separate transduction pathways have been identified. The transient activation of c-Src is involved in cytoskeleton remodeling whereas the Ras pathway controls the transcription of genes such as the transcription factor Slug which is involved in the internalization of desmosomes. These two pathways cooperate to induce the morphological transition, scattering and locomotion of fibroblast-like cells. Growth/scatter factor-producing NBT-II cells are more invasive than cells that do not contain this factor, in orthotopic confrontation assay. In vivo, these cells are very tumorigenic and may confer a more malignant phenotype on parental cells via a community effect. The role of several growth factors and their receptors has been investigated in human bladder carcinomas. A subset of these tumors with poor outcomes produce low levels of FGFR2-IIIb. The synthesis of this receptor de novo in bladder cell lines reduces proliferation in vitro and tumor growth in nude mice. FGFR2-IIIb functions as a tumor suppressor, consistent with the differentiation-inducing capacities of FGF receptors in the suprabasal cells of the skin. FGFR2-IIIb signaling may be involved in the maintenance of E-cadherin, the prototype epithelial adhesion molecule, which is only downregulated in a fraction of tumors with low FGFR2-IIIb synthesis. Human bladder tumors may also activate autocrine loops such as that for EGFR and their ligands, as already demonstrated for murine bladder tumors. Therefore, our results suggest that multifunctional growth factors and their receptors are involved in cell proliferation and epithelial cell plasticity, acting either as positive or negative regulators of tumor progression. The effect on the morphological transition is also clearly relevant to the mechanism governing dissemination and the formation of micrometastatic tumor cells. The extrapolation of these discoveries to human carcinomas should provide markers facilitating the more accurate prediction of the biological behavior of a given tumor and identify clinically and pathologically significant parameters. The identification of critical changes in the growth factor pathways involved in tumor progression will not only provide insight into the genetic and molecular basis of this process, but should also identify targets for new therapies.
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PMID:Epithelial cell plasticity in development and tumor progression. 1050 44

Aberrant activation of hepatocyte growth factor/scatter factor (HGF/SF) and its receptor, Met, is involved in the development and progression of many human cancers. In the screening assay of extracts from the root tuber of Tetrastigma hemsleyanum Diels et Gilg, isoquercitrin inhibited HGF/SF-Met signaling as indicated by its inhibitory activity on HGF/SF-induced cell scattering. Further analysis revealed that isoquercitrin specifically inhibited HGF/SF-induced tyrosine phosphorylation of Met. We also found that isoquercitrin decreased HGF-induced migration and invasion by parental or HGF/SF-transfected bladder carcinoma cell line NBT-II cells. Furthermore, isoquercitrin inhibited HGF/SF-induced epithelial mesenchymal transition in vitro and the invasion/metastasis of HGF/SF-transfected NBT-II cells in vivo. Our data suggest the possible use of isoquercitrin in human cancers associated with dysregulated HGF/SF-Met signaling.
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PMID:Isoquercitrin, ingredients in Tetrastigma hemsleyanum Diels et Gilg, inhibits hepatocyte growth factor/scatter factor-induced tumor cell migration and invasion. 2974 44