Browsing by Subject "Integrins"

Now showing 1 - 7 of 7
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    Co-localization of integrins and matrix metalloproteinases in the extracellular matrix of chondrocyte cultures
    (F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2001) Schulze Tanzil, Gundula; de Souza, P.; Merker, H. J.; Shakibaei, M.
    ß1-int eg rin s we re found in th e ca rtil age matri x, suggesting their implication in the assembly of its architectural sca ffold , but the mechanism fo r this event is not yet clear. Matrix metalloproteinases (MMPs) may be involved in an int egrin -shedding mechanism and matri x 131- integrins may ac t to alter MMP activity. To begin to address this qu esti o n, this stud y was desig ned to determin e wheth er ß1-in teg rin s and MMPs arc colocali zed in th e chondrocy tes or in the ex trace llul ar matrix of cartil age. We investigated high-densit y cultures of limb buds of 12-day -old mo use embryos by double immunoflu o re ce nce, immun oe lectron mi c rosco py and by coimmunoprccipitation assays in order to examine the loca li za ti o n o f ß1-int egrin s and matri x me ta ll oproteinases (MMP-1, MMP-3 and MMP-9) in cartilage. It was found , that all investigated MMPs and 13 1- integrins we re specifically co-loca li zed in high-density cartil age cultures. Immunogold and immunofluorescence labelling of both ß1-integrins and MMPs were observed not only at the surface of chondrocytes but mainl y also in th e pe rice llul ar space a nd distributed be tw ee n coll agen fibrils in th e ex trace llular matrix (ECM) as we ll. Res ults o f immun oprecipitati o n ex pe riments suggest a fun cti onal assoc iati on of MMPs and 13 Lintegrins in chondrocytes as already described fo r other cell types. Further investigations are needed to elu cidate the fun ctional association between Bl-integrins and MMPs in chondrocytes.
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    Extracellular matrix in renal cell carcinomas
    (Murcia : F. Hernández, 1998) Lohi, J.; Leivo, I.; Oivula, J.; Lehto, V.P.; Virtanen, I.
    Extracellular matrix (ECM) may be divided into interstitial matrix and the basement membrane (BM). ECM influences a variety of epithelial cell behaviours, including proliferation, differentiation, and morphogenesis, maybe most widely studied in kidney morphogenesis. In carcinomas, including renal cell carcinomas (RCCs), these properties and interactions of cells with interstitial matrix and BM are disturbed. As a carcinoma with a tendency to spread to distant sites, RCC is an interesting target for the study of epithelialstromal interactions. Among interstitial collagens, type V1 collagen appears to be widely distributed in RCCs. Also EDA-fibronectin (EDA-Fn) as well as tenascin-C (Tn) are important stromal components especially in poorly differentiated carcinomas. BMs of RCC islets and those of tumor blood vessel endothelia may merge in poorly differentiated carcinomas. As a dynamic component of BMs, laminins (Ln) are important in kidney development and RCC progression. Type IV collagen and nidogen, other components of BMs in RCCs, are produced by stromal as well as epithelial cells. ECM proteins may function in RCC progression by binding and regulating the activity of growth factors e.g. transforming growth factor B1 and basic fibroblast growth factor. Also the expression of cell surface receptors for ECM is disturbed in RCCs. At least a, integrin (Int) and CD44 emerge in renal epithelial cells during malignant transformation. Papillary renal neoplasms differ from RCCs by cell adhesion receptor expression and BM composition as well as by ECM avascularity and capacity to bind growth factors, thus suggesting a distinct property for this renal tumor.
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    Focal adhesion kinase: Protein interactions and cellular functions
    (Murcia : F. Hernández, 2002) Abbi, S.; Guan, J.L.
    Integrin-mediated cell adhesion to extracellular matrix (ECM) plays important roles in a variety of biological processes. Recent studies suggested that integrins mediate signal transduction across the plasma membrane via activating several intracellular signaling pathways. Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that has been shown to be a major mediator of integrin signal transduction pathways. Upon activation by integrins, FAK undergoes autophosphorylation as well as associations with several other intracellular signaling molecules. These interactions in the signaling pathways have been shown to regulation a variety of cellular functions such as cell spreading, migration, cell proliferation, apoptosis and cell survival. Recent progress in the understanding of FAK interactions with other proteins in the regulation of these cellular functions will be discussed in this review
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    Regulation of tumor cell invasion by extracellular matrix
    (Murcia : F. Hernández, 1999) Crowe, D.L.; Shuler, C.F.
    The ability of malignant tumor cells to invade normal surrounding tissue contributes in large part to the significant morbidity and mortality of these cancers. The process of invasion involves adherence of the tumor cells to the extracellular matrix (ECM), degradation of matrix components, and movement of the cell body. Attachment to ECM molecules is mediated by the integrin family of extracellular matrix receptors. Integrins are a large family of heterodimeric proteins which transduce a variety of signals from the ECM. Ligand occupancy is critical for activation of integrin signaling. This signaling may occur via several different pathways. One of the best characterized of these pathways is the mitogen activated protein kinase (MAPK) cascade. This serial phosphorylation of substrate proteins terminates in activation of transcription factors which regulate expression of target genes. Many of these genes are critical for extracellular matrix degradation or cell migration. Among these are the matrix metalloproteinases (MMPs), a large family of ECM-degrading enzymes. Regulatory elements in the promoters of MMPs have been characterized, providing insight into how MMP expression is controlled. This review focuses on mechanisms by which the ECM regulates tumor cell invasion through integrin signaling via the MAPK pathway using MMP expression as the model.
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    Roles of integrins in fibronectin matrix assembly
    (Murcia : F. Hernández, 1997) Wu, C.
    Fibronectin (Fn) matrix assembly is a dynamic cellular process in which the soluble dimeric Fn molecules are assembled into insoluble, disulfide bond stabilized fibrillar polymeric matrix. Fn matrix assembly requires specific Fn binding integrins. Several Fn binding integrins that are capable of mediating Fn matrix assembly have been identified. They include a5B1, aIIbB3 and ctvB3 integrins. Cells regulate the matrix assembly process not only by controlling cell surface expression leve1 of the Fn binding integrins but also by modulating Fn binding and cytoskeleton binding activities of the integrins. A major challenge of future studies is to delineate the signal transduction pathway that regulates Fn matrix assembly
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    Tissue remodelling in liver diseases
    (Murcia : F. Hernández, 2003) Giannelli, G.; Quaranta, V.; Antonaci, S.
    Tissue remodelling is a dynamic process that occurs during fetal or adult life and involves a modification of the original organization and function of a tissue. Tissue remodelling is observed in physiological and pathological conditions such as during wound healing or in the mammary gland during the course of pregnancy. In this review we will discuss the remodelling occurring in the liver as a consequence of chronic inflammation, as observed in chronic hepatitis, or as a consequence of hepatocellular carcinoma (HCC) progression in more detail. We will consider how altered deposition and turn-over of extracellular matrix (ECM) proteins could lead to development of liver fibrosis, and how the exacerbation of fibrosis could underlie the development of cirrhosis. The involvement of inflammatory and anti-inflammatory cytokines commonly used as therapeutic agents, such as Interferon-a, is then evaluated with a particular focus on modulation of ECM proteolysis. Finally, we analyze the role of alterations of the surrounding microenvironment including ECM, growth factors, cytokines and membrane receptors for ECM ligands in the development of HCC and in its invasive behaviour.
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    Ultrastructural localization of integrin subunits α α 3 and α α 6 in capillarized sinusoids of the human cirrhotic liver
    (Murcia : F. Hernández, 2011) Quondamatteo, F.; Kempkensteffen, C.; Miosge, N.; Sonnenberg, A.; Herken, R.
    Normal liver sinusoids are not lined by a basement membrane (BM). In contrast, in the course of development of liver cirrhosis, a structured BM is formed de novo in the space of Disse. This BM contributes to the inhibition of the metabolic function of the liver but the pathogenic background of the formation of this perisinusoidal BM is still unclear. Integrins of the ß1-class are generally essential for BM stability and some of them (such as α 2ß1, α 3ß1 and α 6ß1) appear de novo in the perisinusoidal space of the cirrhotic liver. Their cellular distribution in capillarized sinusoids as well as the correlation between their cellular distribution and the formation of the microvascular BM in the cirrhotic liver has not been shown at the ultrastructural level. In the present work we aimed to clarify this issue. We focused on integrins α 3ß1 and α 6ß1 and localised them ultrastructurally in human cirrhotic liver microvessels using postembedding immunogold which allows the ultrastructural localization of antigens with high resolution in the tissue. The newly formed basement membrane of capillarized sinusoids was visualized by means of fixation with addition of tannic acid, which enables the visualization of structures of the extracellular matrix with the highest resolution. Also, we carried out laminin detection using postembedding immunogold. Our results show that both α 3ß1 and α 6ß1 are expressed on the surface of both hepatocytes and endothelial cells, i.e. on both sides of the newly formed basement membrane. This latter shows zones of higher density both in close proximity to the endothelial and to the hepatocytic surfaces which resemble laminae densae. We propose that hepatocytes and endothelial cells may, therefore, by expressing such integrins, contribute to the formation of this pathological BM in the microvessels of the human cirrhotic liver. On stellate cells, which are major producers of BM components, both integrins α 3ß1 and α 6ß1 were also localized.