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)

Two subfragments of laminin, E8, a major part of the long arm, and E1-4, the three short arms, promote cell adhesion and spreading. Three distinct types of adhesive behavior are seen in short term (1 h) assays, typified by secondary murine fibroblasts, adherent only on fibronectin; secondary murine myoblasts, adherent on fibronectin, laminin, and the E8 fragment; and Rugli human glioblastoma cells, adherent on fibronectin, laminin, E8, and E1-4. E8-specific polyclonal antibodies block myoblast adhesion to E8 and to laminin with identical concentration dependence; Rugli binding to E8 but not to laminin is also totally blocked by these antibodies. Heating of E8 and laminin to approximately 60 degrees C abolishes cell attachment-promoting activity for myoblasts. Adhesion of Rugli cells to E8 is also lost, but on laminin the attachment-promoting activity remains constant. This is due to an increase in the activity of E1-4 fragment as it is heated. Thus, major sites for initial cell adhesion to and spreading on laminin lie within the E8 and E1-4 fragments, but not all cells binding to laminin will bind to both fragments. These data may tentatively be explained by the existence of more than one type of receptor for laminin at the cell surface; one is needed for each fragment.
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PMID:Two distinct cell-binding domains in laminin can independently promote nonneuronal cell adhesion and spreading. 303 30

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

We have investigated the effect of integrin antibodies to a well-characterized alpha 5 beta 1 (fibronectin receptor) and to a multi-specific alpha 3 beta 1 (laminin, collagen, and fibronectin receptor), on the expression of matrix metalloproteases and the invasion ability of two human glioblastoma cell lines, SNB19 and U251. Cell adhesion assays indicated that both cell lines adhere to fibronectin, type IV collagen and laminin. Adhesion of cells to fibronectin was inhibited by a RGD peptide. Cells treated with anti-alpha 3 beta 1 or anti-alpha 5 beta 1 antibodies expressed increased levels of MMP-2. An in vitro matrigel assay also showed that the alpha 3 beta 1 antibody-treated cells had greater invasive ability than the controls. Immunofluorescence data showed that glioma cells treated with either anti-alpha 3 beta 1 or anti-alpha 5 beta 1 antibodies expressed diminished alpha 3 beta-1 and alpha 5 beta 1 integrins relative to the controls. The data show that treatment of cells with alpha 3 beta 1 antibody diminishes the integrin expression on the cell surface and increases the MMP-2 activity and invasiveness.
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PMID:Modulation of matrix metalloprotease-2 and invasion in human glioma cells by alpha 3 beta 1 integrin. 863 58

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

The tumor suppressor p16/CDKN2A/INK4a gene is frequently mutated, mostly by homozygous deletions in high-grade gliomas. Although the p16 protein suppresses cell proliferation primarily through inhibition of cell-cycle progression at the G1 phase, other phenotypic changes in glioma cells associated with p16INK4a alterations have not been fully described. To determine the roles of p16 alterations in glioma formation, we have established ecdysone-driven inducible p16 expression in the human glioblastoma cell line CL-4, which were derived from p16-null U87MG cells. Here we show that exogenous p16 expression in CL-4 cells results in morphological changes, with large and flattened cytoplasm, which are associated with increased formation of cytoplasmic actin-stress fibers and vinculin accumulation in the focal adhesion contacts. Adhesion of CL-4 cells to extracellular matrix proteins, such as laminin, fibronectin, and type IV collagen, significantly increased upon exogenous p16 expression, which correlated with increased expression of integrin alpha5 and alphav. Expression of a small GTP-binding protein, Rac, also decreased. Following epidermal growth factor stimulation, phosphorylation of MAP kinases ERK1 and 2 and induction of an early immediate gene product, c-Fos, were significantly reduced in CL-4 cells with p16 expression. These results suggest that the tumor suppressor p16 may exert its antitumor effects through modulation of multiple aspects of glioblastoma phenotypes, including proliferation, invasiveness, and responsiveness to extracellular growth stimuli.
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PMID:Phenotypic changes associated with exogenous expression of p16INK4a in human glioma cells. 1190 77

Malignant gliomas are highly proliferative and invasive tumors with poor prognosis. We investigated the influence of Interferon-gamma (IFN-gamma) on the human malignant glioma cell line A172, measuring cell viability (MTT-test), proliferation (3H-thymidine-uptake), cell death (FACS) adhesion to hyaluronic acid (HA, adhesion-assay) and migration (Boyden-chamber). IFN-gamma significantly decreased cell viability and proliferation. Measured by FACS, an up-regulation of CD95 expression has been shown in combination with an increased rate of cell death, first seen after 96 hours IFN-gamma treatment. Adhesion to HA was decreased after pre-treatment with IFN-gamma. This was not mediated by down-regulation of the main HA-receptor CD44, since IFN-gamma did not change CD44 expression. IFN-gamma-treated cells showed a significantly diminished migration rate through a native or HA-coated 8-microm polycarbonate membrane. To summarise, IFN-gamma influences both the main characteristics of malignancy: it decreases cell proliferation and induces cell death, further it diminishes migration of A172 human glioblastoma cells.
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PMID:Interferon-gamma inhibits growth and migration of A172 human glioblastoma cells. 1191 Dec 81

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

Glioblastoma multiforme is highly aggressive and is the most common glial tumor type. Although there have been advances in treatment, the average survival expectancy is 12-15 months. Several genes have been shown to influence glioblastoma progression. In the present work, we demonstrate that the RhoGTPase Activating Protein 21 (ARHGAP21) is expressed in the nuclear and perinuclear regions of several cell lines. In T98G and U138MG, glioblastoma derived cell lines, ARHGAP21 interacts with the C-terminal region of Focal Adhesion Kinase (FAK). ARHGAP21 depletion by shRNAi in T98G cells alters cellular morphology and increases: FAK phosphorylation states and activation of downstream signaling; the activity state of Cdc42; the production of metalloproteinase 2 (MMP-2) and cell migration rates. These modifications were found to be mainly due to the loss of ARHGAP21 action on FAK and, consequently, the activation of downstream effectors. These results suggest not only that ARHGAP21 might act as a tumor suppressor gene, but also indicate that ARHGAP21 might be a master regulator of migration having a crucial role in controlling the progression of different tumor types.
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PMID:ARHGAP21 modulates FAK activity and impairs glioblastoma cell migration. 1926 1

Glioblastoma represent the most frequent primary tumors of the central nervous system and remain among the most aggressive human cancers as available therapeutic approaches still fail to contain their invasiveness. Many studies have reported elevated expression of the Focal Adhesion Kinase (FAK) protein in glioblastoma, associated with an increase in the rates of both migration and invasion. This designates FAK as a promising target to limit invasiveness in glioblastoma. Thymoquinone (TQ), the main phytoactive compound of Nigella sativa has shown remarkable anti-neoplasic activities on a variety of cancer cells. Here, we studied the anti-invasive and anti-migratory effects of TQ on human glioblastoma cells. The results obtained indicated that TQ treatment reduced migration, adhesion and invasion of both U-87 and CCF-STTG1 cells. This was accompanied by a drastic down-regulation of FAK, associated with a reduction of ERK phosphorylation as well as MMP-2 and MMP-9 secretion. This study provides new data on FAK regulation by a natural product (TQ) which could be of a great value for the development of novel therapies in glioblastoma.
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PMID:Thymoquinone reduces migration and invasion of human glioblastoma cells associated with FAK, MMP-2 and MMP-9 down-regulation. 2217 88

Mammalian Reovirus is a double-stranded RNA virus with a distinctive preference to replicate in and lyse transformed cells. On that account, Reovirus type 3 Dearing (T3D) is clinically evaluated as oncolytic agent. The therapeutic efficacy of this approach depends in part on the accessibility of the reovirus receptor Junction Adhesion Molecule-A (JAM-A) on the target cells. Here, we describe the isolation and characterization of reovirus T3D mutants that can infect human tumor cells independent of JAM-A. The JAM-A-independent (jin) mutants were isolated on human U118MG glioblastoma cells, which do not express JAM-A. All jin mutants harbour mutations in the S1 segments close to the region that encodes the sialic acid-binding pocket in the shaft of the spike protein. In addition, two of the jin mutants encode spike proteins with a Q336R substitution in their head domain. The jin mutants can productively infect a wide range of cell lines that resist wt reovirus T3D infection, including chicken LMH cells, hamster CHO cells, murine endothelioma cells, human U2OS and STA-ET2.1 cells, but not primary human fibroblasts. The jin-mutants rely on the presence of sialic-acid residues on the cell surface for productive infection, as is evident from wheat germ agglutinin (WGA) inhibition experiments, and from the jin-reovirus resistance of CHO-Lec2 cells, which have a deficiency of sialic-acids on their glycoproteins. The jin mutants may be useful as oncolytic agents for use in tumors in which JAM-A is absent or inaccessible.
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PMID:Isolation of reovirus T3D mutants capable of infecting human tumor cells independent of junction adhesion molecule-A. 2311 Jan 75


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