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

Adhesion molecules were studied in regenerating skeletal muscle immunohistochemically and ultrastructurally after a standardized trauma. In normal muscle, extracellular matrix (ECM) protein tenascin was restricted to myotendinous junctions (MTJ), while the integrin beta 1-subunit was present also on the sarcolemma. After injury, tenascin increased on the outer surface of regenerating myofibers, where cellular fibronectin also accumulated. Later, tenascin concentrated at the tips of regenerating myofibers, where new MTJs were formed. The beta 1-subunit disappeared on necrotized myofibers and reappeared on regenerating fibers in a thicker layer. The regenerating myofibers were invested by a basal lamina, except for the growth cones at the distal ends, which were laminin-negative until the formation of MTJs occurred. These results indicate that regenerating muscle cells are attached to the ECM in a way that allows both growth of the muscle cells across the scar and their use before the regeneration is completed.
 ...
PMID:Adhesion in skeletal muscle during regeneration. 137 71

Cell-substratum adhesion strengths have been quantified using fibroblasts and glioma cells binding to two extracellular matrix proteins, fibronectin and tenascin. A centrifugal force-based adhesion assay was used for the adhesive strength measurements, and the corresponding morphology of the adhesions was visualized by interference reflection microscopy. The initial adhesions as measured at 4 degrees C were on the order of 10(-5)dynes/cell and did not involve the cytoskeleton. Adhesion to fibronectin after 15 min at 37 degrees C were more than an order of magnitude stronger; the strengthening response required cytoskeletal involvement. By contrast to the marked strengthening of adhesion to FN, adhesion to TN was unchanged or weakened after 15 min at 37 degrees C. The absolute strength of adhesion achieved varied according to protein and cell type. When a mixed substratum of fibronectin and tenascin was tested, the presence of tenascin was found to reduce the level of the strengthening of cell adhesion normally observed at 37 degrees C on a substratum of fibronectin alone. Parallel analysis of corresponding interference reflection micrographs showed that differences in the area of cell surface within 10-15 nm of the substratum correlated closely with each of the changes in adhesion observed: after incubation for 15 min on fibronectin at 37 degrees C, glioma cells increased their surface area within close contact to the substrate by integral to 125-fold. Cells on tenascin did not increase their surface area of contact. The increased surface area of contact and the inhibitory activity of cytochalasin b suggest that the adhesive "strengthening" in the 15 min after initial binding brings additional adhesion molecules into the adhesive site and couples the actin cytoskeleton to the adhesion complex.
 ...
PMID:Cell adhesion to fibronectin and tenascin: quantitative measurements of initial binding and subsequent strengthening response. 247 81

We have found that endothelial cells adhere much more strongly than fibroblasts to domains of tenascin and fibronectin. Endothelial cells adhered weakly, without spreading, to bacterial expression proteins corresponding to the tenth fibronectin type III (FN-III) domain of fibronectin, which contains the RGD. A larger fibronectin protein, containing this domain and the three amino-terminal 'synergy' domains gave strong adhesion and spreading. Two widely separated domains of tenascin gave adhesion. The third FN-III domain, TNfn3, which contains an RGD sequence in human and chicken tenascin, gave very strong adhesion and spreading of endothelial cells when tested as an isolated domain. Larger segments containing TNfn3 and the adjacent TNfn2 gave weaker adhesion, probably because the RGD sequence is partially blocked. Adhesion to this domain required divalent cations, was exquisitely sensitive to soluble GRGDSP peptide, and was blocked by antisera to the integrin alpha v beta 3. The second tenascin adhesion domain was the fibrinogen-like C-terminal knob, TNfbg. Cells adhered to but did not spread on this domain. This adhesion required divalent cations and was also sensitive to GRGDSP peptide, so it may be mediated by an integrin receptor. We have explored a range of conditions for preparing the adhesion substratum, and our results may resolve the controversy over whether tenascin can act as a substratum adhesion molecule. When coated for short times (1-2 hours) on plastic, tenascin had no adhesion activity, in contrast to fibronectin and the expression proteins, which gave strong adhesion under these conditions. When coated for longer times (12-24 hours) on plastic, the tenascin substratum supported good adhesion, but not spreading, of endothelial cells. Tenascin coated on nitrocellulose gave substantially stronger adhesion than on plastic, but still required long coating times for maximal activity. Adhesion of endothelial cells to native TN was inhibited by GRDGSP peptide. The cell adhesion activity demonstrates the presence on endothelial cells of tenascin receptors, which may play a supportive role in angiogenesis, in the structure of blood vessels, or in binding tenascin to the cell surface to elicit or enhance a signalling function.
 ...
PMID:Endothelial cells adhere to the RGD domain and the fibrinogen-like terminal knob of tenascin. 750 85

Because of the importance of collagens in mediating cell-substrate interactions and the association of collagens with neural recognition molecules in the peripheral nervous system, the ability of neural recognition molecules to modify the substrate properties of collagens, in particular collagen type I, for cell adhesion was determined. Two cell lines, the N2A neuroblastoma and PC12 pheochromocytoma, were investigated for their capacity to adhere to different collagen types in the absence or presence of several neural recognition molecules. Adhesion of N2A or PC12 cells and membrane vesicles from PC12 cells to collagen type I was reduced when the collagen had been preincubated prior to its application as substrate with the extracellular domain of myelin-associated glycoprotein (s-MAG) or, as control, fibroblast tenascin-C (F-tenascin). In mixture with other collagen types, s-MAG was only able to reduce the adhesiveness of collagen types III and V, but not of collagen types II and IV. F-tenascin reduced the adhesiveness of all collagen types tested. In contrast to F-tenascin, s-MAG had to be present during fibrillogenesis to exert its effect, indicating that it must be coassembled into the collagen fibril to block the binding site. Cell adhesion to collagen type I was dependent on Mg2+ or Mn2+ and inhibited by a monoclonal antibody to the alpha 1 integrin subunit. The combined observations indicate that s-MAG and F-tenascin interfere with cell binding, most probably by modifying the integrin binding site, and that the two molecules act by different mechanisms, both leading to reduction of adhesion.
 ...
PMID:Recognition molecules myelin-associated glycoprotein and tenascin-C inhibit integrin-mediated adhesion of neural cells to collagen. 754 51

Tenascin, an extracellular matrix protein, is expressed in human gliomas in vitro and in vivo. The distribution of tenascin at the invasive edge of these tumors, even surrounding solitary invading cells, suggests a role for this protein as a regulator of glioma cell migration. We tested whether purified tenascin, passively deposited on surfaces, influenced the adhesion or migration of a human gliomaderived cell line, SF-767. Adhesion of glioma cells to tenascin increased in a dose-dependent fashion up to a coating concentration of 10 micrograms/ml. Higher coating concentrations resulted in progressively fewer cells attaching. Cell adhesion could be blocked to basal levels using anti-beta 1 integrin antibodies. In contrast, when anti-alpha v antibodies were added to the medium of cells on tenascin, cell adhesion was enhanced slightly. Using a microliter scale migration assay, we found that cell motility on tenascin was dose dependently stimulated at coating concentrations of 1 and 3 micrograms/ml, but migration was inhibited below levels of non-specific motility when tested at coating concentrations of 30 and 100 micrograms/ml. Migration on permissive concentrations of tenascin could be reversibly inhibited with anti-beta 1, while treatment with anti-alpha v antibodies increased migration rates. We conclude that SF-767 glioma cells express two separate integrin receptors that mediate contrasting adhesive and migratory responses to tenascin.
 ...
PMID:Contrasting migratory response of astrocytoma cells to tenascin mediated by different integrins. 885 12

Mesothelial cells (MC) form a polarized monolayer lining serosal cavities. During serositis, the MC lining undergoes hyperplasia, and MC are shed into effusions. During these processes, contact with basement membrane and, ultimately, neighboring cells is at least temporarily lost, suggesting regulated alterations in cell/matrix and cell/cell adhesion. Such interactions are primarily mediated by integrins. Malignant mesothelioma has a growth pattern characterized by lateral, limited invasive but contiguous spread. During serositis, activated MC, both sessile and detached, expressed an extended spectrum of beta1, beta3 and beta4 integrins compared with resting MC, as shown by immunohistology. Malignant mesothelioma had an integrin repertoire and a subcellular distribution resembling that of activated sessile rather than floating MC. In vitro, MC exposed a more comprehensive pattern of integrins than that of the newly established mesothelioma cell lines ME-HD-1 and ME-HD-2, as shown by flow cytometry. MC consistently adhered better than mesothelioma cells to laminin, tenascin, fibronectin and collagen type IV. Adhesion of MC and mesothelioma cells to these matrix proteins was, at least in part, mediated via beta1 integrins. The different integrin profiles and adhesion properties of cultured MC and mesothelioma cells may reflect a limited functional differentiation of the latter.
 ...
PMID:Pleural mesothelioma mimics the integrin profile of activated, sessile rather than detached mesothelial cells. 921 27

Osteopontin is an RGD-containing glycoprotein that mediates adhesion and migration of a variety of different cell types. We recently showed that a recombinant osteopontin fragment that was expected to be formed following thrombin cleavage was not only biologically active, but also could support alpha 9 beta 1-mediated adhesion, an activity not found in the full-length molecule. In this study we defined binding sites on the N-terminal osteopontin fragment important for alpha 9 beta 1-mediated cell interactions. In addition to adhesion, we showed that alpha 9 beta 1 could mediate cell migration, a function not previously identified for this integrin. Using site-directed mutagenesis, we made specific mutations in the RGD region of the N-terminal osteopontin fragment. Mutation of RGD to RGE resulted in a 50% decrease in cell adhesion. The residual binding to the RGE mutant could be blocked by alpha 9 and beta 1 antibodies. Adhesion to the RGE mutant was due to residual recognition of the RGE site by alpha 9 beta 1 since mutants containing more drastic mutations in the RGD domain achieved by mutating RGD to RAA or by eliminating the RGD completely failed to support cell adhesion and migration. In contrast, alpha 9 beta 1-mediated adhesion to tenascin was RGD independent. These data demonstrate that alpha 9 beta 1 is one of the few integrin receptors that can interact with two distinct RGD-containing ligands through different adhesive domains.
 ...
PMID:Structural requirements for alpha 9 beta 1-mediated adhesion and migration to thrombin-cleaved osteopontin. 966 32

Multiple myeloma represents a human B cell malignancy which is characterized by a predominant localization of the malignant cell clone within the bone marrow. With the exception of the terminal stage of the disease the myeloma tumor cells do not circulate in the peripheral blood. The bone marrow microenvironment is believed to play an important role in homing, proliferation and terminal differentiation of myeloma cells. Here we have studied the expression of several extracellular matrix (ECM) molecules in the bone marrow of multiple myeloma patients and analyzed their adhesive capacities with four different human myeloma-derived cell lines. All ECM molecules analyzed (tenascin, laminin, fibronectin, collagen types I, III, V and VI) could be detected in bone marrow cryostat sections of multiple myeloma patients. Adhesion assays showed that only laminin, the microfibrillar collagen type VI and fibronectin were strong adhesive components for the myeloma cell lines U266, IM-9, OPM-2 and NCI-H929. Tenascin and collagen type I were only weak adhesive substrates for these myeloma cells. Adhesion to laminin and fibronectin was beta 1-integrin-mediated since addition of anti-beta 1-integrin antibodies could inhibit the binding of the four different cell types to both matrix molecules. In contrast, integrins do not seem to be involved in binding of the myeloma cells to collagen type VI. Instead, inhibition of binding by heparin suggested that membrane-bound heparan sulfate proteoglycans are responsible ligands for binding to collagen type VI. Adhesion assays with several B-cell lines resembling earlier differentiation stages revealed only weak interactions with tenascin and no interactions with collagen type VI, laminin or fibronectin. In summary, the interactions of human myeloma cells with the extracellular matrix may explain the specific retention of the plasma cells within the bone marrow.
 ...
PMID:Adhesive interactions of human multiple myeloma cell lines with different extracellular matrix molecules. 976 71

Adhesion is a process that can be divided into three separate stages: (1) cell attachment, (2) cell spreading, and (3) the formation of focal adhesions and stress fibers. With each stage the adhesive strength of the cell increases. De-adhesion can be defined as the process involving the transition of the cell from a strongly adherent state, characterized by focal adhesions and stress fibers, to a state of intermediate adherence, represented by a cell that is spread, but that lacks stress fibers terminating at adhesion plaques. We propose that this modification of the structural link between the actin cytoskeleton and the extracellular matrix results in a more malleable cellular state conducive for dynamic processes such as cytokinesis, mitogenesis, and motility. Anti-adhesive proteins, including thrombospondin, tenascin, and SPARC, rapidly signal de-adhesion, potentially mediating proliferation and migration during development and wound healing. Intracellular signaling molecules involved in the regulation of de-adhesion are only beginning to be identified. Interestingly, many of the same signaling proteins recognized to play important roles during the process of adhesion have also been found to act during de-adhesion. Characterization of the precise mechanisms by which these signals modulate adhesive structures and the cytoskeleton will further our understanding of the regulation of adhesive strength and its function in cellular physiology.
 ...
PMID:Signaling of de-adhesion in cellular regulation and motility. 985 39

Retinal pigment epithelial cell malfunction is a causative feature of age-related macular degeneration, and transplantation of new retinal pigment epithelial cells is an attractive strategy to prevent further progression and visual loss. However, transplants have shown limited efficacy, mainly because transplanted cells fail to adhere and migrate onto pathological Bruch's membrane. Adhesion to Bruch's membrane is integrin-mediated. Ageing of Bruch's membrane leads to a decline in integrin ligands and, added to this, wet age-related macular degeneration leads to upregulation of anti-adhesive molecules such as tenascin-C. We have therefore investigated whether manipulation of integrin function in retinal pigment epithelial cells can restore their adhesion and migration on wet age-related macular degeneration-damaged Bruch's membrane. Using spontaneously immortalized human retinal pigment epithelial cells (adult retinal pigment epithelium-19), we show that adhesion and migration on the Bruch's membrane components is integrin-dependent and enhanced by integrin-activating agents manganese and TS2/16. These allowed cells to adhere and migrate on low concentrations of ligand, as would be found in aged Bruch's membrane. We next developed a method for stripping cells from Bruch's membrane so that adhesion and migration assays can be performed on its surface. Integrin activation had a moderate effect on enhancing retinal pigmented epithelial cell adhesion and migration on normal human and rat Bruch's membrane. However, on Bruch's membrane prepared from human wet age-related macular degeneration-affected eyes, adhesion was lower and integrin activation had a much greater effect. A candidate molecule for preventing retinal pigmented epithelial interaction with age-related macular degeneration-affected Bruch's membrane is tenascin-C which we confirm is present at high levels in wet age-related macular degeneration membrane. We show that tenascin-C is anti-adhesive for retinal pigmented epithelial cells, but after integrin activation, they can adhere and migrate on it using alphaVbeta3 integrin. Alternatively, we find that transduction of retinal pigmented epithelial cells with alpha9 integrin, a tenascin-C-binding integrin, led to a large increase in alpha9beta1-mediated adhesion and migration on tenascin-C. Both expression of alpha9 integrin and integrin activation greatly enhanced the ability of retinal pigment epithelial cells to adhere to tenascin-rich wet age-related macular degeneration-affected Bruch's membranes. Our results suggest that manipulation of retinal pigment epithelial cell integrins through integrin activating strategies, or expression of new integrins such as alpha9, could be effective in improving the efficacy of retinal pigment epithelial cell transplantation in wet age-related macular degeneration-affected eyes.
 ...
PMID:Integrin activation or alpha 9 expression allows retinal pigmented epithelial cell adhesion on Bruch's membrane in wet age-related macular degeneration. 2015 68


1 2 Next >>