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Query: UMLS:C0001511 (Adhesion)
 5,955 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Glutamine supplementation has been advocated for patients requiring parenteral nutritional support. However, the direct effect of glutamine on neoplastic cells is poorly understood. We therefore investigated the effects of glutamine on the proliferation, differentiation, and cell-matrix interactions of two human colon carcinoma cell lines (Caco-2 and SW620) adapted to glutamine-free media. Doubling times were calculated by logarithmic transformation of serial cell counts. Alkaline phosphatase, cathepsin C (dipeptidyl peptidase), lactase, and isomaltase expression (markers of differentiation) were assayed by digestion of synthetic substrates. Adhesion to matrix proteins was assessed by colorimetric quantitation of toluidine blue staining of adherent cells. Surface expression of Caco-2 receptors for matrix proteins (integrins) was studied by biotinylation and immunoprecipitation with specific antibodies. Glutamine (1-10 mM) dose-dependently stimulated Caco-2 proliferation on all matrices studied with maximal effect at 7 mM. For instance, Caco-2 doubling time on collagen IV decreased by 57 +/- 0.2% (SE) (P < 0.001). Glutamine inhibited the expression of all four digestive enzymes with maximal inhibition ranging from 10 to 40% (P < 0.05 for all). Adhesion to matrix proteins was markedly diminished (51 +/- 1%, P < 0.01) by glutamine (5 mM) treatment, correlating with decreased alpha 2 and beta 1 integrin subunit surface expression. Glutamine had similar effects on SW620 cells, stimulating proliferation, inhibiting digestive enzyme expression, and diminishing both adhesion and integrin surface expression. Glutamine supplementation modulates the phenotype of at least two human colon carcinoma cell lines, increasing proliferation, decreasing differentiation, and decreasing adhesion to matrix proteins in association with decreased integrin expression. Although the mechanisms of these effects await elucidation, such characteristics would appear to predict more aggressive tumor behavior and raise the possibility that nutritional supplementation with glutamine may be deleterious in patients with cancer.
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PMID:Glutamine modulates phenotype and stimulates proliferation in human colon cancer cell lines. 795 30

The ligand specificity of the alpha 3A beta 1 integrin was analyzed using K562 cells transfected with full-length alpha 3A cDNA and was compared with that of alpha 6A beta 1 in similarly transfected K562 cells. Clones were obtained that showed comparable surface expression of either alpha 3A beta 1 or alpha 6A beta 1 integrins. Those expressing alpha 3A beta 1 attached to and spread on immunopurified human kalinin and cellular matrices containing human kalinin, which is a particular isoform of laminin. In addition, alpha 3A transfectants adhered to bovine kidney laminins possessing a novel A chain variant. Binding to kalinin was blocked by a monoclonal antibody against the A chain constituent of kalinin and adhesion to both kalinin and kidney laminins by anti-alpha 3 and beta 1 monoclonal antibodies. The alpha 3A transfected cells bound more strongly to kalinin and bovine kidney laminins after treatment with the beta 1 stimulatory antibody TS2/16. A distinctly weaker and activation-dependent adhesion of alpha 3A transfectants was observed on human placental laminins possessing the Am chain variant (merosin), and no adhesion occurred on bovine heart laminins and murine EHS tumor laminin. Further inactive substrates were fibronectin, nidogen, and collagen types IV and VI, indicating that the alpha 3A beta 1 integrin is a much less promiscuous receptor than thought before. By contrast, alpha 6A transfected cells adhered to all laminin isoforms when stimulated with TS2/16. Adhesion also occurred only on bovine kidney laminins in the absence of TS2/16. These results demonstrate that both alpha 3A beta 1 and alpha 6A beta 1 integrins are typical laminin receptors but that their affinity and activation dependence for binding to various laminin isoforms differ considerably.
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PMID:Distinct and overlapping ligand specificities of the alpha 3A beta 1 and alpha 6A beta 1 integrins: recognition of laminin isoforms. 801 6

We have investigated the role of alpha 4 beta 1 and alpha 5 beta 1 integrins in adhesion and migration of T lymphocytes to extracellular matrix proteins. Fibronectin, collagen type IV, and laminin promoted haptotactic and chemotactic migration of lymphoid T cell lines and 12-O-tetradecanoylphorbol 13-acetate-stimulated blood lymphocytes, as determined using a modified Boyden chamber system. Adhesion studies of the T cell lines indicated involvement of both alpha 4 beta 1 and alpha 5 beta 1 integrins in the binding to fibronectin. In contrast, migration assays demonstrated that haptotactic and chemotactic migration to fibronectin in most cases was mediated by only one of the beta 1 integrins. FACS analysis demonstrated comparable amounts of alpha 4 beta 1 and alpha 5 beta 1 on the various cell lines, indicating that utilization of the integrins for migration is not determined by their expression on the cells. Haptotactic migration toward a 120-kDa fibronectin fragment containing the RGD sequence, confirmed the selectivity of the different beta 1 integrins in directing migration. Thus, T cells using alpha 5 beta 1 for haptotaxis against fibronectin were migrating against the 120 kDa fragment whereas T cells using alpha 4 beta 1 were not. These results indicate that the response of T cells to haptotactic and chemotactic signals usually is mediated selectively via alpha 4 beta 1 or alpha 5 beta 1 although binding of fibronectin to the cells is not restricted to only one of the integrins. Cholera toxin and 8-Br-cAMP but not pertussis toxin inhibited migration of T cell lines to fibronectin. Adhesion of these cells to fibronectin was not influenced by any of the toxins. Thus, both in their integrin utilization and in their signaling pathways, adhesion and migration show substantial differences in T cells.
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PMID:Functional specialization of fibronectin-binding beta 1-integrins in T lymphocyte migration. 802 66

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

E- and P-cadherin are calcium (Ca2+)-dependent cell adhesion molecules important in the morphogenesis and maintenance of skin structure. By use of flow cytometry and specific antibodies, we now show that cultured human melanocytes express E- and P-cadherin on their surfaces, and that these molecules have the same characteristics as reported for other cell types. Specifically, melanocyte cadherins are sensitive to trypsin digestion in the absence of Ca2+ and are protected from trypsin degradation by Ca2+, and are functional at 37 degrees C but not at 4 degrees C. We further show that melanocytes contain mRNA transcripts encoding both E- and P-cadherin. Adhesion of cultured melanocytes to keratinocyte monolayers is abolished by pre-treatment of the melanocytes with trypsin/EDTA, which degrades E- and P-cadherins, is greatly reduced by anti-E-cadherin antibodies and is slightly reduced by antibodies to P-cadherin, alpha 2, alpha 3 and beta 1 integrins. In contrast to normal melanocytes, eight of nine melanoma cell lines lacked E-cadherin (or expressed markedly reduced levels) and five were negative for P-cadherin. Melanoma cells also failed to adhere to keratinocyte monolayers. These results demonstrate that normal human melanocytes express functional E- and P-cadherin and that E-cadherin is primarily responsible for adhesion of human melanocytes to keratinocytes in vitro. In addition, transformed melanocytes express markedly reduced levels of E- and P-cadherin, and exhibit decreased affinity for normal keratinocytes in vitro, suggesting that loss of cadherins may play a role in melanoma metastasis.
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PMID:E-cadherin is the major mediator of human melanocyte adhesion to keratinocytes in vitro. 805 51

Adhesion of human neuroblastoma cells (SK-N-SH clone SY5Y) to laminin or collagen type IV promotes tyrosine phosphorylation of a group of proteins with molecular mass ranging from 100 to 130 kDa and of a protein of 180 kDa. The same pattern of tyrosine phosphorylation was observed when SY5Y cells were allowed to adhere to culture dishes coated with monoclonal antibodies directed to the integrin subunits expressed in the cells, alpha 1, alpha 3, and beta 1, indicating that these receptors are responsible for this signaling mechanism. Using specific antibodies we identified the focal adhesion kinase p125FAK as a component of the 100- to 130-kDa phosphoproteins. Treatment with genistein or herbimycin A, two specific tyrosine kinase inhibitors, greatly reduced the tyrosine phosphorylation of the 100- to 130- and the 180-kDa proteins in response to laminin or collagen IV. Concomitantly, neurite outgrowth on the matrix proteins was strongly inhibited. This effect was observed in two distinct neuroblastoma cell lines, SY5Y and SK-N-BE. Genistein and herbimycin A treatment did not affect cell viability nor cause retraction of preformed neurites. These data suggest that matrix-induced tyrosine phosphorylation events are involved in neurite extension.
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PMID:Role of tyrosine phosphorylation in matrix-induced neurite outgrowth in human neuroblastoma cells. 808 34

Kalinin was purified from squamous cell carcinoma (SCC25) spent culture media using an immunoaffinity column prepared from the mAb BM165. The affinity-purified material was separated by SDS-PAGE into three bands of 165-155, 140, and 105 kD identical to those obtained from normal human keratinocyte cultures and previously identified as kalinin. Kalinin promoted adhesion of a large number of normal cells and established cell lines with an activity similar to other adhesion molecules such as the laminin-nidogen complex, fibronectin, or collagen IV. However, kalinin was a much better substrate than laminin-nidogen complex for adhesion of cells of epithelial origin including primary human keratinocytes. Adhesion to kalinin was followed by cell shape changes ranging from rounded to fully spread cells depending on the cell types. The adhesion-promoting activity of kalinin was conformation dependent and was abolished by heat denaturation. mAb BM165 prevented cell adhesion to kalinin but not to other extracellular matrix substrates. However, either complete or partial inhibition was observed with different cells suggesting the existence of at least two cell-binding sites on the kalinin molecule. Experiments inhibiting cell adhesion with function-blocking anti-integrin subunit antibodies indicated that both alpha 3 beta 1 and alpha 6 beta 1 integrins are involved in the cellular interactions with kalinin, while for cell adhesion to classical mouse Engelbreth-Holm-Swarm laminin only alpha 6 beta 1 integrins, and not alpha 3 beta 1, appeared to be functional. Altogether, these results suggest that kalinin may fulfill additional functions than laminin, particularly for epithelial cells.
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PMID:Kalinin is more efficient than laminin in promoting adhesion of primary keratinocytes and some other epithelial cells and has a different requirement for integrin receptors. 813 72

Previously, we have establish K562 transfectants that express either alpha 6A beta 1 or alpha 6B beta 1 (K alpha 6A or K alpha 6B) on their surface. Both cell lines bind to laminin and kalinin after treatment with the beta 1-stimulatory antibody TS2/16. Here we introduce the full-length beta 4 cDNA into the alpha 6A- and alpha 6B-expressing K562 cells and selected stably transfected cells. The beta 4 subunit was expressed on the surface of both transfectants and it formed dimers with the alpha 6A or alpha 6B subunits. Immunoprecipitation and preclearing analyses revealed that both transfectants expressed alpha 6 beta 1, in addition to alpha 6 beta 4. While K alpha 6A and K alpha 6B cells required TS2/16 stimulation for binding to laminin or kalinin, adhesion of the unstimulated beta 4-transfected K alpha 6A and K alpha 6B cells to these matrix components was already substantial. This adhesion was mediated by both alpha 6 beta 1 and alpha 6 beta 4 since it was completely blocked by an alpha 6-specific antibody or by a combination of anti-beta 1 and anti-beta 4 antibodies, but only partially by either of these latter two antibodies alone. Adhesion to laminin was completely blocked by an antiserum to laminin fragment E8 as was the adhesion to kalinin by an antibody to kalinin, demonstrating the specificity of adhesion. Both transfectants always adhered more strongly to kalinin than to laminin. Furthermore, binding to kalinin was less well blocked by antibodies to beta 4 than binding to laminin, indicating that the affinity of alpha 6 beta 4 for kalinin is higher than that for laminin. The fact that alpha 6 beta 1 mediated adhesion without TS2/16 stimulation on the beta 4-transfected K alpha 6A and K alpha 6B cells suggests that some activation of alpha 6 beta 1 had occurred in these cells, even though binding was increased when they were actively stimulated by the antibody TS2/16. Finally, we show that Mn2+ induced binding of solubilized alpha 6 beta 4 to matrix containing kalinin, deposited by the murine cell line RAC-11P/SD. This binding was inhibited by the anti-alpha 6 mAb GoH3. Together, these results indicate that both alpha 6 beta 1 and alpha 6 beta 4 are receptors for laminin and kalinin and that there are no differences in ligand specificity between the A and B variants of the alpha 6 subunit when associated with either beta 1 or beta 4.
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PMID:The alpha 6 beta 4 integrin is a receptor for both laminin and kalinin. 814 84

Osteoclast interaction with extracellular matrix drives the sequential events that end with bone resorption. However, the role of matrix proteins is not yet fully understood. We studied this problem on human osteoclast-like cells derived from giant cell tumors of bone (GCT cells). On GCT cells we considered cytoskeletal organization, adhesion properties, and integrin expression upon plating in serum-free medium onto fibronectin (FN), collagen (COL), thrombospondin (TSP), bone sialoprotein (BSPII), and osteopontin (OPN). GCT cells promptly adhered and spread on FN, BSPII, and OPN, while only 50% adhered on COL and none on TSP. The integrin beta 1 chain was always associated to focal adhesions, while the alpha v beta 3 heterodimer was detected in focal contacts only upon plating on BSPII, OPN, and FN. The focal clustering of beta 1 was impaired by monensin treatment, indicating that endogenous FN secretion was required to drive beta 1 into focal contacts. Conversely, alpha v beta 3 clustering was also not affected by monensin when cells were plated onto plasma FN. Immunoprecipitation of metabolically labeled GCT cell lysates showed that three different heterodimers (alpha v beta 3, alpha 3 beta 1, and alpha 5 beta 1) were assembled. Adhesion to FN was completely inhibited by beta 1 antibodies at dilutions up to 1:400, while beta 3 antibodies, at similar dilutions, impaired spreading but not adhesion. We conclude that alpha v beta 3 is the main integrin used by GCT cells in bone recognition. We also suggest that selected substrata may induce the release and the organization of endogenous FN that eventually drives the recruitment of a beta 1 integrin receptor into focal contacts.
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PMID:Adhesion properties and integrin expression of cultured human osteoclast-like cells. 818 15

The mechanisms responsible for the accumulation of eosinophils at sites of allergic and other inflammatory reactions are unknown, but recent studies have implicated both eosinophil and endothelial adhesion molecules in this process. However, less well studied have been the adhesive interactions between eosinophils and the subendothelial basement membrane and interstitial connective tissues. To test the hypothesis that eosinophils might interact with extracellular matrix proteins, we analyzed purified human eosinophils for the expression and function of various beta 1 integrins. Using indirect immunofluorescence and flow cytometry, purified eosinophils from mildly allergic donors were found to consistently express the integrin subunits beta 1 (CD29), alpha 4 (CD49d, very late activation antigen [VLA]-4 alpha), and alpha 6 (CD49f, VLA-6 alpha). No significant expression of the alpha 1, alpha 2, alpha 3, alpha 5, or beta 4 subunits was detected. Platelet contamination of the eosinophil preparations was excluded by light microscopy and by the inability to detect expression of platelet glycoproteins alpha v, CD41b, and CD42b. Immunoprecipitation and sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of eosinophils confirmed the expression of cell-surface beta 1, alpha 4, and alpha 6. Furthermore, eosinophils purified from allergic donors were shown to adhere to plate-bound laminin, but not to type 1 or type 4 collagen. Adhesion to laminin was concentration-dependent, required divalent cations, and was completely and specifically inhibited by the anti-alpha 6 monoclonal antibody (MoAb) GoH3 and by the anti-beta 1 MoAb 33B6. Interestingly, the anti-beta 1 MoAb 18D3 (which like 33B6 blocks eosinophil binding to VCAM-1) did not inhibit eosinophil adhesion to laminin, suggesting that there are functionally distinct epitopes on the beta 1 subunit. Eosinophils purified from 4 healthy, nonallergic donors also showed alpha 6-dependent adhesion to laminin, although these cells adhered less well. These studies establish the expression of alpha 6 beta 1 on human eosinophils and document its function as a laminin receptor. Interaction of eosinophil alpha 6 beta 1 with laminin, eg, in basement membranes, may contribute to the localization of these cells at inflammatory sites in vivo.
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PMID:Expression of a functional laminin receptor (alpha 6 beta 1, very late activation antigen-6) on human eosinophils. 821 35


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