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)

Adhesion molecules can improve hematopoietic cell survival; however, their role in leukemic cell resistance to drug-induced apoptosis is poorly documented. The CD44 adhesion molecule is strongly expressed on acute myeloid leukemia (AML) blasts. Using 2 myeloid cell lines, HL60 and NB4, evidence is presented that prior incubation with the CD44-specific monoclonal antibody (mAb) A3D8, reported to induce differentiation of AML blasts, significantly decreases apoptosis induced by 3 drugs used in AML chemotherapy: daunorubicin (DNR), mitoxantrone, and etoposide. In addition, in HL60 cells, CD44 ligation with A3D8 mAb fully abrogates the DNR-triggered generation of ceramide, a lipid second messenger involved in the DNR apoptotic signaling pathway. Moreover, results show that the A3D8 mAb and Bcl-2 additively inhibit DNR-induced apoptosis in HL60 cells overexpressing Bcl-2. These results suggest that, to eradicate AML blasts, the differentiation-inducing anti-CD44 mAb A3D8 should not be administered prior to apoptosis-inducing drugs.
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PMID:Ligation of the CD44 adhesion molecule inhibits drug-induced apoptosis in human myeloid leukemia cells. 1091 Sep 43

Adhesion molecules regulate the migration of lymphocytes in lymphoid and non-lymphoid organs. In the lung, little is known about lymphocyte sticking and migration through the pulmonary vascular endothelium in physiological or pathological situations. Therefore the isolated buffer-perfused rat lung was used to investigate the mobilization of lymphocytes out of the normal lung into the venous effluent and to the bronchoalveolar space. The lymphocyte subset composition was characterized in the venous effluent, the lung tissue and the bronchoalveolar lavage (BAL) using immunocytology. Lymphocytes continuously left the normal lung at a total of 5.0 +/- 0.7 x 106 cells within the first hour of perfusion. The injection of 200 x 106 lymphocytes via the pulmonary trunk increased the venous release of lymphocytes by 170%. To investigate the effect of LFA-1 and CD44 on the adhesion of lymphocytes to the pulmonary endothelium, lymphocytes preincubated with an anti-LFA-1 MoAb, which blocks the interaction of LFA-1 and intercellular adhesion molecule-1 (ICAM-1), or lymphocytes preincubated with an anti-CD44 MoAb, were injected. The injection of LFA-1-blocked lymphocytes led to an increase by 70% of injected cells recovered in the perfusate within the first hour, whereas anti-CD44 treatment of injected lymphocytes had no effect. The LFA-1-blocked lymphocytes showed higher numbers of T and B cells in the effluent. Thus, the present experiments demonstrate that LFA-1 influences the trapping of lymphocytes in the vasculature of the healthy rat lung.
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PMID:Blockade of leucocyte function-associated antigen-1 (LFA-1) decreases lymphocyte trapping in the normal pulmonary vasculature: studies in the isolated buffer-perfused rat lung. 1093 Nov 56

Graves' ophthalmopathy (GO) is thought to result from a complex interplay of genetic and environmental factors. Various genes, including those coding for HLA, may determine a patient's susceptibility to the disease and its severity, but in addition, numerous and often unknown environmental factors may determine its course. Once established, the chronic inflammatory process within the orbital tissues appears to take on a momentum of its own. Based upon our current state of knowledge, we propose the working scheme shown in Fig. 1 for the pathogenesis of GO: Against the background of a permissive immunogenetic milieu, circulating T cells in patients with Graves' Disease (GD), directed against certain antigens on thyroid follicular cells, recognize antigenic epitopes that are shared by tissues contained in the orbital space. Here, preadipocytes and fibroblasts most likely act as target and effector cells of the orbital immune process. This includes preadipocyte fibroblasts present in the perimysium of extraocular muscles, which do not appear to be immunologically or metabolically different from those located in the orbital connective tissue. Differentiation of orbital preadipocyte fibroblasts into mature adipocytes expressing increased levels of TSHR may be driven by stimulation with circulating or locally produced cytokines or effectors. To date, it is still unknown how autoreactive T cells escape deletion by the immune system and become directed against a self-antigen that is presented by cells residing in the thyroid gland and in certain extrathyroidal locations. Mimicry of a host antigen by a microorganism or presentation of an altered self-antigen may promote proliferation and expansion of autoreactive T cell clones. T cell recruitment into the orbital tissues is facilitated by certain chemokines and cytokines, which help to attract T cells by stimulating the expression of several adhesion molecules (e.g. ICAM-1, VCAM-1, CD44) in vascular endothelium and connective tissue cells. Adhesion molecules are known to be important for a variety of interactions between immunocompetent cells, connective tissue cells and extracellular matrix components. In addition, these molecules play a central role in lymphocyte activation and localization, facilitating antigen recognition, T cell costimulation, and various effector-target cell functions at the inflammatory sites, many of which result in amplification of the cellular immune process in active GO. Analysis of variable region genes of T cell antigen receptors in orbital T cells of patients with active GO has revealed limited variability of TcR V gene usage, suggesting that antigen-driven selection and/or expansion of specific T cells may occur during the early stages of GO. T cells and macrophages populate the orbital space and release a number of cytokines (most likely a Th-1-type spectrum) into the surrounding tissues. Cytokines, oxygen free radicals and fibrogenic growth factors, released both from infiltrating inflammatory and residential cells, act upon orbital preadipocytes in a paracrine and autocrine manner to stimulate adipogenesis, fibroblast proliferation, glycosaminoglycan synthesis, and the expression of immunomodulatory molecules. Smoking, a well-known aggravating factor in GO with an uncertain mode of action, may aggravate tissue hypoxia and exert important immunomodulatory effects. Finally, the long-held hypothesis of a thyroid cross-reactive antigen within the orbital tissues has recently gained significant support from an animal model of ophthalmopathy, and from in vitro and ex vivo studies. If confirmed by immunological studies, these data may well explain the localized infiltration of the orbital tissues by autoreactive lymphocytes that share intriguing molecular features with intrathyroidal lymphocytes. Local release of certain cytokines, TSHR-directed autoantibodies, or other factors might further enhance adipogenesis, glycosaminoglycan synthesis and expression of
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PMID:Thyroid-associated eye disease. 1098 Jun 91

Adhesion molecules such as CD44 play an important role in the metastatic cascade by mediating tumor cell interaction with the endothelium and the subendothelial matrix. As a so-called "lymphocyte homing receptor," CD44 is physiologically involved in migration of circulating lymphocytes to lymphatic tissue. In the present study, we investigated the expression of CD44v3 and v6 in 237 patients with stage IB, N0 cervical carcinoma by means of immunohistochemistry. These results were correlated with the GOG score and other prognostic variables. Median follow-up was 82.6 months (39-110 months). Thirty-nine patients recurred and 35 died from disease within the observation period. In univariate analysis, the GOG score, histologic subtype, and CD44v6 expression were statistically significant predictors for poor overall survival (OS). In multivariate (Cox regression) analysis, the GOG score (< 40 vs. 40-120, RR: 1.37 (95% CI: 1.10-1.71); 40-120 vs. > 120, RR: 2.23 (95% CI: 1.28-3.88); P = 0.004), histologic subtype (adenosquamous carcinomas) (RR: 4.56 (95% CI: 1.49-13.92), P = 0.007) and CD44v6 expression (RR: 2.42 (95% CI: 1.14-5.10), P = 0.021) were independent predictors for poor OS. The expression of CD44v3 did not correlate with prognosis. Furthermore we found a strong correlation between CD44v6 expression and lymphovascular space invasion (LVSI) (chi2 = 17.01, P = 0.0001). Tumor expansion into the loco-regional lymphatic system is the preferred way of tumor spread in cervical carcinoma. The strong correlation of CD44v6 with LVSI produces a significant degree of suspicion that cervical carcinoma cells expressing CD44v6 could, by mimicking lymphocytes, exploit their pathways.
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PMID:CD44v6 expression is an independent prognostic factor in node-negative FIGO stage IB cervical carcinoma. 1124 Jul 59

Adhesion and proteolysis are basic reactions of tumor growth and metastasis. During these complex processes malignant cells change their adhesion behaviour and proteolytic capacity. Therefore, an extensive characterization of tumor cells is necessary if results of functional assays e.g., tests for tumor cell invasion are to be correlated with the presence of tumor antigens. This paper describes the detection of CD44 variant sequences, urokinase-type plasminogen activator (uPA) and uPA-receptor (uPAR) by immunoluminescence and activity measurements. For these investigations the melanoma cell line IGR 1 was used. The expression of CD44 (v5), uPA and uPAR on the cell surface was shown by indirect labelling with monoclonal antibodies (mAb). The marker enzyme horseradish peroxidase (HRP) of the secondary Ab was used to release luminescence and fluorescence with suitable substrates. The enhanced luminescent assay was superior to fluorescence analysis. uPA-activity in intact cells was examined with the substrates plasminogen, Z-Gly-Gly-Arg-AMC and Z-Lys-SBzl including selective inhibitors. The immunoluminescent assay can be alternatively used with well-tried immunofluorescent methods e.g. flow cytometry, for the detection of cellular cancer markers (1).
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PMID:Co-localization of CD44 and urokinase-type plasminogen activator on the surface of human melanoma cells. 1132 65

The effect of CD44-phenotypic expression on metastasis to the lung was studied using a spontaneous murine osteosarcoma-derived cell line, POS-1, stimulated with lipopolysaccharide (LPS). POS-1 cells were inoculated into the hind paws of 20 C3H/HeJ mice and produced a visible mass in all mice in 5 weeks, and these transplanted tumors resulted in lung metastasis in all mice. The number of metastatic foci in the lungs was 12.0+/-2.1 (mean+/-SD) with LPS-stimulated cells, which was significantly higher than that of unstimulated cells (5.8+/-1.4; N=10 for each; P<0.05). Hyaluronate (HA), a ligand of CD44, inhibited a number of lung metastases in a dose-dependent manner (0.5% HA, 3.0+/-1.1; 0.005% HA, 5.1+/-1.5; without HA, 8.6+/-1.7; N=10 for each; P<0.05, each group with HA versus the group without HA). Adhesion assay by coculturing POS-1 cells and lung microvascular endothelial cells on culture plate showed that the adhesion was significantly lower in HA treated POS-1 than those without HA (1.18+/-0.12 and 2.74+/-0.17, respectively, P<0.05). These results suggest that lung metastasis was accelerated by up-regulation of CD44.
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PMID:Acceleration of lung metastasis by up-regulation of CD44 expression in osteosarcoma-derived cell transplanted mice. 1146 96

Graves' ophthalmopathy is thought to result from a complex interplay of genetic and environmental factors. Various genes including those coding for HLA may determine a patient's susceptibility to the disease and its severity, but in addition numerous and often unknown environmental factors may determine its course. The orbital immune process is thought to be initiated, on the background of a permissive immunogenetic milieu, by circulating T cells directed against certain antigens on thyroid follicular cells that also recognize antigenic epitopes which are shared by tissues contained in the orbital space. Analysis of variable region genes of T cell antigen receptors in orbital T cells of patients with active Graves' ophthalmopathy has revealed limited variability of TcR V gene usage, suggesting that antigen-driven selection and/or expansion of specific T cells may occur during the early stages of Graves' ophthalmopathy. T cell recruitment into the orbital tissues is facilitated by certain chemokines and cytokines, which attract T cells by stimulating the expression of several adhesion molecules (e.g. ICAM-1, VCAM-1, CD44) in vascular endothelium and connective tissue cells. Adhesion molecules are known to be important for a variety of interactions between immunocompetent cells, preadipocyte fibroblasts and adipocytes. In addition, these molecules play a central role in lymphocyte activation and localization, facilitating antigen recognition, T cell costimulation, and various effector-target cell functions at the inflammatory sites, which result in amplification of the cellular immune process in active Graves' ophthalmopathy. T cells and macrophages populate the orbital space and release a number of cytokines (most likely a Th-1-type spectrum) into the surrounding tissues. Cytokines, oxygen free radicals and fibrogenic growth factors, released both from infiltrating inflammatory and residential cells, act upon orbital preadipocytes in a paracrine and autocrine manner to stimulate adipogenesis, fibroblast proliferation, glycosaminoglycan synthesis, and the expression of immunomodulatory molecules. Smoking, a well-known aggravating factor in Graves' ophthalmopathy, may aggravate tissue hypoxia and exert important immunomodulatory and pro-oxidant effects. Differentiation of orbital preadipocyte fibroblasts into mature adipocytes expressing increased levels of TSHR may also be driven by stimulation with circulating or locally produced cytokines or effectors. TSHR-directed autoantibodies or T cells may thus play a direct role promoting adipogenesis, glycosaminoglycan synthesis and expression of immunomodulatory proteins within the orbits. Once the net effect of these changes has come to increase the volume of the fatty connective tissues within the orbit, then proptosis, extraocular muscle dysfunction, and periorbital congestion will ensue.
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PMID:[Interactions of fibroblasts, adipocytes and immunocompeent cells in the pathogenesis of endocrine ophthalmopathy]. 1159 97

The initial adhesion of transplanted chondrocytes to surrounding host cartilage may be important in the repair of articular defects. Adhesion may position cells to secrete molecules that fill the defect and integrate repair tissue with host tissue. While chondrocytes are known to become increasingly adherent to cartilage with time, the molecular basis for this is unknown. The objective of this study was to investigate the role of beta1-integrin, CD44, and annexin V receptors in chondrocyte adhesion to cartilage. Chondrocytes were cultured in high density monolayer, released with trypsin, and allowed to recover in suspension for 2 h at 37 degrees C. Under these conditions, flow cytometry analysis showed that chondrocytes expressed beta1-integrins, CD44, and annexin V. In a rapid screening assay to assess chondrocyte adhesion to cartilage, cell detachment decreased from 79% at 10 min following transplantation to 10% at 320 min. Treatment of cells with a monoclonal antibody to block beta1-integrins significantly increased chondrocyte detachment from cartilage compared to untreated controls. Similarly, results from a parallel-plate shear flow adhesion assay showed that blocking beta1-integrins significantly increased chondrocyte detachment from cartilage compared to untreated controls at each level of applied shear (0-70 Pa). In both assays, treatment of cells with reagents that block CD44 (hyaluronan oligosaccharides or monoclonal Ab IM7) or annexin V (polyclonal Ab #8958) had no detectable effect on adhesion. With cartilage treated with chondroitinase ABC, blocking beta1-integrins also increased chondrocyte detachment, while blocking CD44 and annexin V also had no detectable effect. Under the conditions studied here, beta1-integrins appear to mediate chondrocyte adhesion to a cut cartilage surface. Delineation of the mechanisms of adhesion may have clinical implications by allowing cell manipulations or matrix treatments to enhance chondrocyte adhesion and retention at a defect site.
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PMID:Mechanisms of chondrocyte adhesion to cartilage: role of beta1-integrins, CD44, and annexin V. 1178 Oct 14

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

Collagen is a multifunctional protein, serving as a structural scaffold and a modulator of cellular responses. Prior work has identified distinct regions from several collagen types that promote cell adhesion, spreading, migration, and signal transduction. One of these regions, alpha1(IV)1263-1277 from type IV collagen, mediates these responses via melanoma cell CD44-chondrotin sulfate proteoglycan receptors. In the study presented here, we have used a triple-helical model of alpha1(IV)1263-1277 to evaluate (a) conformational stability and (b) cellular responses based on single-site incorporation of trans-4-fluoro-L-proline (trans-Flp) or cis-4-fluoro-L-proline (cis-Flp) for trans-4-hydroxy-L-proline (trans-Hyp). The structural effects of cis-Flp and trans-Flp substitution were studied by circular dichroism and NMR spectroscopies. The peptide containing a single trans-Flp instead of trans-Hyp was slightly more thermally stable than the parent peptide (T(m) = 37 vs 34 degrees C), while the peptide containing cis-Flp was considerably less stable than the parent peptide (T(m) = 30 degrees C). Melanoma cell adhesion and spreading were examined under conditions where the trans-Hyp-, trans-Flp-, and cis-Flp-containing ligands were approximately 15, <10, and approximately 65% denatured, respectively. Adhesion to each of the three ligands was remarkably sensitive to the respective ligand conformation, with EC(50) values of approximately 2.5, approximately 0.35, and >5.0 microM for the trans-Hyp-, trans-Flp-, and cis-Flp-containing ligands, respectively. Melanoma cell spreading was quantitated over a ligand concentration range of 0.01-50 microM and, in a fashion similar to adhesion, was more extensive on the trans-Flp ligand than on the trans-Hyp ligand. Very low levels of spreading were observed with the cis-Flp-containing ligand at all concentrations tested. Melanoma cell adhesion to and spreading on the three ligands suggested the dramatic biological consequence of even subtle changes in relative triple-helical content. Such subtle changes may model those occurring in the basement membrane during the tumor cell invasion process, and thus provide mechanistic insight into this stage of metastasis.
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PMID:Modulation of triple-helical stability and subsequent melanoma cellular responses by single-site substitution of fluoroproline derivatives. 1199


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