Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001511 (Adhesion)
 5,955 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A unique characteristic of astrocytic malignancies is their frequent dissemination through the brain. Cellular determinants of migration include adhesion to the substratum, restructuring of the actin cytoskeleton to generate motion, and (in the setting of invasion into tissue) secretion of enzymes for remodeling interstitial space to accommodate forward motion of the migrating cell. In order to better understand these features in the context of local brain invasion by astrocytoma cells, the adhesion and migratory properties of these cells have been investigated in an in vitro monolayer system. Adhesion of 8 different astrocytoma cell lines to different purified human extracellular matrix (ECM) proteins (collagen type IV, cellular fibronectin, laminin, and vitronectin) revealed that there is no "astrocytoma-specific" ECM protein that consistently leads to high cell binding. Similarly, migration of astrocytoma cells was found to be variable and dependent on different ECM proteins. Laminin was frequently the most permissive for adhesion and migration. Adhesion to collagen, fibronectin, and vitronectin was integrin dependent and could be blocked using anti-beta 1 integrin antibodies; in contrast, attachment to laminin could not be blocked using these antibodies. A comparison of adhesion with migration for each of the cell lines on each of the 4 ECM proteins revealed that poor adhesion was associated with minimal migration and that frequently, high adhesion was correlated with rapid migration. When tested for migration on autologous, cell-derived ECM, none of the cell lines were as migratory as they were on one of the purified ECM proteins, with the exception of SF767 cells. Furthermore, it was found that ECM from SF767 cells promoted the migration of other astrocytoma cells. The results from this study indicate that migration is a constitutive behavior of glioma cells which is dependent on, or modified by, the presence or absence of permissive ligands in the environment.
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PMID:Determinants of human astrocytoma migration. 803 13

We studied the immunohistochemical expression of integrin alpha and beta chains in the normal and neoplastic human brain. Normal astrocytes expressed alpha 2, alpha 3, alpha 6, beta 1, and beta 4 chains in some areas facing major interstitial tissues, but they were consistently negative for the other integrins examined (alpha 4, alpha 5, alpha V, alpha L, alpha M, alpha X, beta 2, beta 3). Neoplastic astrocytes in vivo and in vitro showed increased expression of alpha 3 and beta 1, and some also of alpha 5, alpha V, beta 3, and beta 4. Neoexpression of alpha 4 and reduced levels of beta 4 were detected in glioblastoma vascular proliferations compared with normal endothelial cells. Oligodendroglioma, ependymoma, choroid plexus papilloma, pituitary adenoma, and meningioma cells showed the same integrin pattern as their normal counterparts. Adhesion assays using the astrocytoma cell lines U-138 MG and U-373 MG revealed strong attachment to collagen types I to VI and undulin, which was inhibited by antibodies to beta 1, but not by those to alpha 2, alpha 3, alpha 6, and alpha V. We conclude that astrocytomas show increased levels or neoexpression of various integrins and strong attachment to various extracellular matrix components, which appears to be almost exclusively mediated by beta 1-integrins.
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PMID:Characterization of integrin receptors in normal and neoplastic human brain. 831 46

The extracellular domain of receptor protein tyrosine phosphatase beta (RPTPbeta) is composed of several domains which mediate its interactions with distinct ligands present on the surface of either neurons or glial cells. Here, we demonstrate that the fibronectin type III domain (FNIII) of RPTPbeta binds to glial tumor-derived cell lines and primary astrocytes. We used affinity purification to isolate several proteins that specifically bind to the FNIII domain of RPTPbeta. One of these, a 240 kDa protein that was purified from U118MG glioblastoma cell, was identified as tenascin C based on the amino acid sequence of several tryptic peptides. The interaction of RPTPbeta with tenascin C was found to mediate cell adhesion. Adhesion and spreading of SF763T astrocytoma cells expressing RPTPbeta on tenascin C was specifically abolished by the addition of a soluble fragment containing the FNIII domain of the receptor. RPTPbeta-dependent cell adhesion was mediated by binding to the alternatively spliced FNIII repeats A1,2,4 (TnfnA1,2,4) of tenascin C. Furthermore, COS cells expressing RPTPbeta adhere to TnfnA1,2,4, while the parental cells did not. These results demonstrate that the FNIII domain of RPTPbeta binds to tenascin C and suggest that RPTPbeta present on glial tumor cells is a primary adhesion receptor system to the extracellular matrix.
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PMID:Glial tumor cell adhesion is mediated by binding of the FNIII domain of receptor protein tyrosine phosphatase beta (RPTPbeta) to tenascin C. 1131 93

Tenascin-C is an adhesion-modulating extracellular matrix molecule that is highly expressed in tumor stroma and stimulates tumor cell proliferation. Adhesion of T98G glioblastoma cells to a fibronectin substratum is inhibited by tenascin-C. To address the mechanism of action, we performed a RNA expression analysis of T89G cells grown in the presence or absence of tenascin-C and found that tenascin-C down-regulates tropomyosin-1. Upon overexpression of tropomyosin-1, cell spreading on a fibronectin/tenascin-C substratum was restored, indicating that tenascin-C destabilizes actin stress fibers through down-regulation of tropomyosin-1. Tenascin-C also increased the expression of the endothelin receptor type A and stimulated the corresponding mitogen-activated protein kinase signaling pathway, which triggers extracellular signal-regulated kinase 1/2 phosphorylation and c-Fos expression. Tenascin-C additionally caused down-regulation of the Wnt inhibitor Dickkopf 1. In consequence, Wnt signaling was enhanced through stabilization of beta-catenin and stimulated the expression of the beta-catenin target Id2. Finally, our in vivo data derived from astrocytoma tissue arrays link increased tenascin-C and Id2 expression with high malignancy. Because increased endothelin and Wnt signaling, as well as reduced tropomyosin-1 expression, are closely linked to transformation and tumorigenesis, we suggest that tenascin-C specifically modulates these signaling pathways to enhance proliferation of glioma cells.
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PMID:Growth promoting signaling by tenascin-C [corrected]. 1549 59

We report on a pedigree with a pair of brothers each with minor anomalies, developmental delay, and autistic-symptoms who share an unbalanced translocation (not detectable by karyotype). The unbalanced translocation involves a 7.1 Mb loss of the terminal portion of 10q, and a 4.2 Mb gain of 11q. One of the brothers also developed a cerebellar juvenile pilocytic astrocytoma. The father was found to be a balanced carrier and the couple had a previous miscarriage. We demonstrate that the breakpoint for the triplicated region from chromosome 11 is adjacent to two IgLON genes, namely Neurotrimin (NTM) and Opioid Binding Protein/Cell Adhesion Molecule-like (OPCML). These genes are highly similar neural cell adhesion molecules that have been implicated in synaptogenesis and oncogenesis, respectively. The children also have a 10q deletion and are compared to other children with the 10q deletion syndrome which generally does not involve autism spectrum disorders (ASDs) or cancer. Together these data support a role for NTM and OPCML in developmental delay and potentially in cancer susceptibility.
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PMID:An unbalanced translocation involving loss of 10q26.2 and gain of 11q25 in a pedigree with autism spectrum disorder and cerebellar juvenile pilocytic astrocytoma. 2349 67