ISSN:1422-6405    

DOI:10.1159/000147841

出版商:S. Karger AG    

年代:1996

数据来源: Karger

ISSN:1422-6405    

DOI:10.1159/000147842

出版商:S. Karger AG    

年代:1996

数据来源: Karger

ISSN:1422-6405    

DOI:10.1159/000147843

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

Transformation of an epithelial sheet into a migrating mesenchymal cell population implies the destruction of the basal lamina underlying the epithelium, and the subsequent localized digestion of the extracellular matrix by the migrating cells. Proteases are involved in these processes. Among them, molecules containing both a serine protease domain and at least one kringle domain have been identified as possible important effectors. Interestingly, related proteins containing an inactive serine protease domain also seem to play a role, suggesting that the function of these molecules in epithelial-mesenchymal transformation is not confined to proteolytic digestion of cell attachments. Instead, these molecules act through specific tyrosine kinase receptors in the membrane of the responding cells. In this review, we summarize data implicating this family of molecules in various epithelial-mesenchymal transitions during embryonic development. Our major focus of attention are: hepatocyte growth factor/scatter factor (HGF/SF), its tyrosine kinase receptor proto-oncogene c-met, and the related peptide factor HGF-like/macrophage-stimulating protein (HGF1/MSP), whose receptor is the Ron tyrosine kinase, c-met and Ron also have another close homolog in the chick, called Sea, whose ligand remains unknown. Interestingly, HGF/SF is activated by other plasminogen-related molecules which, apart from a specific activator, include the protease urokinase. HGF/SF, c-met and HGF/MSP are expressed in dynamic ways during early embryonic development, correlating with regions undergoing epithelial/mesenchymal transformations. Moreover, several assays are now starting to reveal great pleiotropism of function during development, including both the loss and the acquisition of epithelial morphology according to the cell type and assay used, as well as angiogenesis, kidney tubule morphogenesis, cell motility, the maintenance of competence for neural induction and some aspects of the later development of the musculoskeletal and nervous systems.

ISSN:1422-6405    

DOI:10.1159/000147844

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

Cardiac morphogenesis proceeds from a sequential series of epithelial-mesenchymal transitions which begins by establishing bipotential heart-forming cells and later their segregation into endocardial and myocardial lineages. Cells within each lineage integrate to form two concentric epithelia which inductively interact to transform cells of the inner epithelium, the endocardium, into mesenchymal or ‘cushion’ cells. Noncardiogenic epithelia (dorsal mesocardium, epicardium, neural ectoderm and coelomic mesothelium) undergo transition into populations of extracardiac mesenchyme that combine over time with cushion tissue to remodel the simple tubular heart into a four-chambered organ. Model systems are described for studying the mechanisms of cardiac-related transformations including primary cultures of precardiac epithelia and a differentiation-inducible, avian stem cell line called QCE-6. Focus is centered on the molecular mechanism by which endocardial epithelium transforms into cushion mesenchyme. Experimental findings are reviewed and interpreted in the context of a hypothetical model that seeks to answer why only some cells within an epithelium transform and whether the transformation process is regulated by intrinsic or extrinsic mechanisms. The model proposes that epithelial cells competent to transform to mesenchyme express characteristic markers including receptors for extrinsic signals secreted by stimulator cells (e.g. myocardium). Candidate extrinsic signals include multicomponent complexes called adherons. If applied directly to cultured endocardium, myocardial adherons but not those secreted by L6 myoblasts, induce changes in gene expression within target endocardial cells for proteases and cellxell and celkmatrix adhesion molecules that accompanied transformation to mesenchyme. A main component of myocardial adherons has been identified as ES antigens, one of which, ES/130, has been cloned, found to have a novel sequence and in culture assays shown to be required for endocardium to transform to mesenchyme. The spatiotemporal pattern of ES protein expression within the embryo suggests that common mechanisms may exist for embryonic epithelial-mesenchymal transformati

ISSN:1422-6405    

DOI:10.1159/000147845

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

Kidney epithelia have two separate origins. Collecting ducts develop in the manner of most glandular organs, by growth and branching of a bud derived from a pre-existing epithelium. Excretory tubules develop by a direct mesenchyme to epithelium transition (MET), which is induced by the tips of the developing collecting duct system as it invades a specialised area of mesenchymal cells. The process by which these metanephrogenic mesenchyme cells achieve MET can be divided into several stages; induction, acquisition of stem cell character, fate determination, condensation, epitheliogenesis, polarisation and maturation. Progress through these stages is regulated by ‘checkpoints’ at which permission to proceed requires specific signals. The stages of development are characterised by the expression of new combinations of genes that code for transcription factors (Hox genes, Pax genes, zinc finger proteins), signalling effectors (growth factors, Wnts, receptor tyrosine kinases) and morphoregulatory molecules (CAMs, cadherins, extracellular matrix ligands). This review summarises current knowledge about the molecular interactions that control MET in the kidney, and also about how their failure might result in Wilms’ tumour, one of the most common cancers of chil

ISSN:1422-6405    

DOI:10.1159/000147846

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

Embryo implantation in higher primates is mediated by trophoblast: in the earliest phases by syncytiotrophoblast, then by both cytotrophoblast and syncytiotrophoblast. In the course of placentation three main trophoblast populations can be identified: cytotrophoblast stem cells and two differentiated derivative cell types: the syncytiotrophoblast and the extravillous cytotrophoblast. The syncytiotrophoblast remains mainly epithelial while the extravillous cytotrophoblast undergoes an epithelial-mesenchymal transition (EMT), initially forming multi-layered cell columns and then, in human, infiltrating deeply the maternal decidual stroma and blood vessels. Finally, some infiltrating cells differentiate further to become giant cells of the placental bed and myometrium. During the course of these events the extravillous cytotrophoblast acquires a distinct phenotype, losing some typical epithelial components (e.g. E-cadherin, integrin a6(34), but retaining others (e.g. cytokeratins). The signals that trigger this EMT are not well understood but its realisation is of critical importance for pregnancy success.

ISSN:1422-6405    

DOI:10.1159/000147847

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

Epithelial cells are the most important cell type in the development of human malignancies. More than 90% of all malignant tumors are carcinomas, and thus of epithelial origin. Aberrant growth and the ability to invade the underlying tissues are intrinsic properties of the fatally altered cells. Multiple genetic alterations that can influence growth and genetic stability of the carcinoma cells have been characterised during tumor progression. Loss of epithelial morphology and the acquisition of mesenchymal characteristics are typical for carcinoma cells late in tumor progression and correlate with metastatic potential. In vitro, epithelial-mesenchymal transitions can be induced by interference with the integrity of the adherens junction, by signalling via tyrosine kinases, and by oncogene expression. In carcinoma cells, loss or downregulation of E-cadherin expression are frequently observed in carcinomas, and correlate with the malignancy of the tumor. In general, this change in expression is regulated at the transcriptional level. However, tumor types or cell lines exist which show mesenchymal characteristics but nevertheless express E-cadherin protein or mRNA. A more-detailed analysis demonstrated that other mechanisms that interfere with E-cadherin-mediated cell adhesion can be operative. Mutations in the E-cadherin gene and loss or mutation of the second, intact copy as well as mutation in the catenin genes, which encode proteins that interact with the cytoplasmic portion of E-cadherin, can be observed. In addition, transient or unregulated phosphorylation by receptor tyrosine kinases or oncogenic tyrosine kinases, respectively, can interfere with the epithelial morphology and induce a mesenchymal conversion. Since tyrosine phosphorylation of β-catenin correlates with the epithelial-mesenchymal transition that is observed, E-cadherin-mediated cell adhesion might be modulated by such a mechanism. Interestingly, the same molecules implicated in the control of malignant properties turn out to play fundamental roles in the control of normal epithelial growth, differentiation and morphogenesis

ISSN:1422-6405    

DOI:10.1159/000147848

出版商:S. Karger AG    

年代:1996

数据来源: Karger

摘要:

This contribution discusses which factors bring about the transformation of epithelium to mesenchyme. Amongst biological agents which have this role are a number of cytokines (e.g. EGF, FGF-1, TGF-β, HGF/SF) and extracellular matrix macromolecules, such as collagens. The coordinated changes in cell morphology, associated with the induction of cell motility and the loss of intercellular junctions, are under the control of signaling molecules that transduce the signal emanating from the plasma membrane, which ultimately lead to changes in gene expression

ISSN:1422-6405    

DOI:10.1159/000147849

出版商:S. Karger AG    

年代:1996

数据来源: Karger

ISSN:1422-6405    

DOI:10.1159/000147850

出版商:S. Karger AG    

年代:1996

数据来源: Karger