Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0029463 (osteosarcoma)
 16,637 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Several receptors for the extracellular matrix protein collagen have been described which belong to the superfamily of receptors collectively known as integrins. Although several integrins have been shown to interact with extracellular matrix molecules via a common recognition site, arginine-glycine-aspartic Acid (RGD), within the beta 1 integrin subfamily, only the fibronectin receptor (alpha 5 beta 1) has been convincingly shown to interact with RGD. In the present study, we tested whether a collagen receptor could interact with RGD. Adhesion of an osteosarcoma cell line, MG-63, to immobilized collagen I was inhibited by the cyclic RGD-containing peptide, C*GRGDSPC* (where C* indicates that Cys participates in disulfide), and not by the linear GRGDSP or the non-RGD-containing cyclic peptide, C*GKGESPC*. Similarly, using collagen-Sepharose affinity chromatography, a heterodimeric protein could be specifically eluted from the column by the cyclic RGD peptide. Immunoprecipitations of the eluted material with monoclonal antibodies showed reactivity with the collagen receptor alpha 2 beta 1 and not alpha 3 beta 1. Our data demonstrate that RGD peptides can interact with the collagen receptor, and the differences seen with the linear and cyclic peptide suggest that the cyclic C*GRGDSPC* has a higher avidity for the receptor than the more flexible linear GRGDSP. In this paper, we provide supportive evidence that one possible mode of collagen interaction with alpha 2 beta 1 is via the RGD recognition sequence.
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PMID:The collagen receptor alpha 2 beta 1, from MG-63 and HT1080 cells, interacts with a cyclic RGD peptide. 133 Oct 77

Activation of endothelial cells by the two inflammatory mediators interleukin-1 (IL-1) and tumor necrosis factor strongly increases tumor cell adhesion. We describe antibody inhibition studies showing that the endothelial leukocyte adhesion molecule-1 (ELAM-1), a cell-surface glycoprotein selectively expressed by cytokine-activated endothelial cells and responsible for neutrophil adhesion, is the major, if not the only, mediator of colon carcinoma cell adhesion to activated endothelial cells. Among the different tumor cell lines tested, seven colon carcinoma cell lines were sensitive to ELAM-1 antibodies. Adhesion of melanoma, osteosarcoma, and lung, cervix, or kidney carcinoma cell lines to IL-1-treated endothelial cells was not affected by the ELAM-1 antibody. This result suggests that ELAM-1 is selectively recognized by colon carcinoma cells and that adhesion of tumor cells to activated endothelial cells could be mediated by different and specific mechanisms.
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PMID:Tumor cell adhesion to endothelial cells: endothelial leukocyte adhesion molecule-1 as an inducible adhesive receptor specific for colon carcinoma cells. 171 24

We investigated the effects of beta 1 integrins on tumor cell (TC) adhesion to unstimulated and interleukin-1 (IL-1) activated endothelial cells (EC). IL-1 treatment (20 units/ml for 6 hours) of cultured human umbilical vein EC significantly increased adhesion of seven human TC lines of different origin. A goat antiserum raised to purified alpha 5 beta 1 integrin abolished the IL-1 induced increment in adhesion of two osteosarcomas, one melanoma, one lung, and one kidney carcinoma, whereas it did not affect adhesion of two colon carcinoma cell lines. Further studies were performed on MG63 osteosarcoma cells. Adhesion of MG63 osteosarcoma cells to EC was dependent on time of EC treatment with IL-1: it was maximal at 12 hours and declined at 24 hours. alpha 5 beta 1 antiserum blocked IL-1 induced increase in MG63 adhesion at any time of EC treatment. This effect appears to be mainly directed to MG63 integrins since selective incubation of the antiserum with EC, but not with MG63, did not modify TC adhesion. Using a series of antibodies to different alpha and beta chains, we found that only monoclonal antibodies (mAb) to alpha 4, alpha 5, and beta 1 could inhibit MG63 adhesion to IL-1 activated EC, whereas alpha 2, alpha 6, and beta 3 antibodies were ineffective. Antibodies to fibronectin had very little activity on MG63 adhesion to EC matrix and did not significantly affect MG63 adhesion to control or IL-1 treated EC. Antibodies to alpha 4, alpha 5, and beta 1 were only partially effective in inhibiting MG63 adhesion to EC matrix. These data indicate that the capacity of alpha 4 beta 1 and alpha 5 beta 1 integrins to bind fibronectin contributed very little to MG63 adhesion to EC. The importance of beta 1 integrins in promoting a direct interaction between EC and MG63 was further shown by inhibition of rosette formation among these cells in suspension by the alpha 5 beta 1 antiserum. Only a VCAM-1/INCAM110 mAb, but not ELAM-1 or ICAM-1 mAbs, could inhibit MG63 adhesion to IL-1 activated EC. Overall these data indicate that at least two members of the beta 1 integrin subfamily (alpha 4 beta 1 and alpha 5 beta 1) are involved in MG63 adhesion to cytokine treated EC. This integrin function might be important at early stages of TC interaction with the vessel wall.
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PMID:Role of beta 1 integrins in tumor cell adhesion to cultured human endothelial cells. 175 2

Prolonged glucocorticoid treatment causes osteoporosis in vivo and inhibits bone formation in vitro. We have previously shown that glucocorticoids inhibit calcification and alter osteoblast organization in a mineralizing bone organ culture system. In this study, the effect of glucocorticoids on osteoblast adhesion to bone matrix proteins and integrin expression was examined in primary rat osteoblasts and a transformed rat osteosarcoma-derived cell line ROS 17/2.8. After 24 h of treatment with corticosterone, these cells displayed a concentration-dependent decrease in adhesion to type I collagen and fibronectin. Adhesion was significantly decreased as early as 4 h after glucocorticoid administration. With 100 nM corticosterone treatment for 24 h, inhibition of the adhesion of ROS 17/2.8 cells and primary osteoblasts to fibronectin was 75 +/- 10% and 50 +/- 8%, and inhibition of adhesion to collagen was 31 +/- 10% and 65 +/- 5%, respectively. This effect was specific for osteoblasts, because glucocorticoids did not change the adhesion of fibroblasts. However, glucocorticoids did inhibit the adhesion of all cell types to rat osteonectin. To determine whether the change in osteoblast attachment to collagen and fibronectin was due to an alteration in integrin levels, the plasma membranes of these cells were labeled with [125I]lactoperoxidase, solubilized, and immunoprecipitated with an antibody to beta 1. A 24-h treatment with 100 nM corticosterone caused 80 +/- 2% and 64 +/- 9% decreases in beta 1 levels in primary osteoblasts and ROS 17/2.8 cells, respectively. These results were confirmed with immunofluorescence microscopy, which showed a glucocorticoid-induced decrease in beta 1 staining. Treatment of primary rat osteoblasts and ROS 17/2.8 cells for 72 h with corticosterone also decreased beta 1-integrin messenger RNA levels in a dose-dependent manner. We have demonstrated that the inhibition of integrin expression by glucocorticoids is involved in the decrease in osteoblast adhesion to bone extracellular matrix proteins. These data suggest that integrin modulation may influence osteoblast function and bone formation and, thus, contribute to glucocorticoid-induced osteoporosis.
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PMID:Glucocorticoids inhibit the attachment of osteoblasts to bone extracellular matrix proteins and decrease beta 1-integrin levels. 753 Jun 48

The response of human MG-63 osteosarcoma cells to physiological levels of hydrostatic pressure was studied. Cell cultures were subjected to a 20-min, 4-MPa hydrostatic pressure pulse. Adhesion was measured at 20 min and 2 h post-hydrostatic pressure. Morphometric measurements of cell shape and immunofluorescent assays of cytoskeletal and adhesion proteins were done pre- and post-hydrostatic pressure. Pressure-treated cells showed increased adhesion (resistance to deadhesion by trypsinization)-with increased recovery time. Indirect immunofluorescence demonstrated increased heterotypic adhesion receptor at cell-cell interfaces and increased alpha 3, beta 1-integrin at cell-substrate interfaces. Indirect immunofluorescence demonstrated depolymerization of alpha-tubulin, vimentin, and actin during the pressure pulse. Actin reorganization was slower than that of alpha-tubulin and vimentin, with stress filaments not well organized even after 1 h postpressure. The depolymerization of alpha-tubulin, vimentin, and actin observed at relatively low levels of hydrostatic pressure suggests disintegration of the integrin-cytoskeletal attachment complex. The increased resistance of the cells to trypsinization and the increase in both heterotypic adhesion receptor and the alpha 3, beta 1-integrin at cell interfaces suggest that cells compensate for loss of cytoskeletal integrity by increasing attachment to both adjacent cells and the extracellular matrix.
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PMID:Physiological levels of hydrostatic pressure alter morphology and organization of cytoskeletal and adhesion proteins in MG-63 osteosarcoma cells. 832 74

Ganglioside GD1a, which is highly expressed in poorly metastatic FBJ-S1 cells, has been shown to inhibit the serum-induced migration capability of highly metastatic FBJ-LL cells. In the present study, the capacity of FBJ-S1 cells to adhere to vitronectin was found to be about half that of FBJ-LL cells. Pre-treatment of FBJ-LL cells with GD1a decreased this capacity by 30% that of the control, whereas GM1-pre-treatment caused only a 10% decrease, indicating that GD1a specifically inhibits FBJ-LL cell adhesion to vitronectin. Since FBJ-LL cells contain almost no GD1a, transfectants capable of expressing GD1a to varying degrees were produced in this study by transfection of FBJ-LL cells with GM2/GD2-synthase cDNA. Decrease in the serum-induced migration capacity of these transfectants was accompanied by an increment in GD1a expression. Adhesion of the transfectants to vitronectin decreased by 30% as compared with mock-transfected cells. Within 4 to 5 weeks after GD1a-expressing transfectant and mock-transfected cells were transplanted into mice, metastatic nodules were observed in liver, lung, kidney and adrenal glands of mock-transplanted mice, but not in those with GD1a-expressing transfectants, indicating that GD1a suppresses the metastasis of FBJ-osteosarcoma cells, possibly by inhibiting cell migration and cell adhesion. The involvement of the ganglioside in the suppression of metastasis is clearly demonstrated in the present study.
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PMID:Suppression by ganglioside GD1A of migration capability, adhesion to vitronectin and metastatic potential of highly metastatic FBJ-LL cells. 1052 8

Increased activity, membrane association, and secretion of cathepsin B have been shown to correlate positively with invasiveness and the metastatic properties of many tumor entities. Cathepsin B is able to directly facilitate invasion by degrading extracellular matrix components or to indirectly facilitate invasion by activating other matrix-degrading proteases like the urokinase-type plasminogen activator. To investigate the role of cathepsin B in bone tumor invasion, the osteosarcoma cell line MNNG/HOS was stably transfected with an expression vector capable of expressing the antisense cDNA transcript of cathepsin B. Five stably transfected antisense cell clones, the control (vector) cell clones, and the parental cells were characterized. At first, the stable incorporation of the constructs was demonstrated by Southern blot analysis. In ELISA assays, all antisense clones showed a significant reduction at the cathepsin B antigen level (about 70%) as compared with the control cell clones and MNNG/HOS. Similar results were obtained for cathepsin B activity in the antisense-transfected cells. In the antisense cell clones, Northern blot analysis and reverse transcription-PCR revealed a considerable decrease of approximately 50% in the levels of cathepsin B mRNA. Expression of cathepsins L and K (sequence homologies) was not affected. The invasive potential and migration of untransfected and transfected tumor cell clones in vitro were analyzed in Transwell chambers. Antisense-transfected cells showed a markedly lower invasion and motility than did MNNG/HOS and the controls. Adhesion to collagen I and matrigel matrices was not affected. These results demonstrate that cathepsin B is involved in the complex proteolytic processes in invasive osteosarcomas.
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PMID:Inhibitory effects of antisense cathepsin B cDNA transfection on invasion and motility in a human osteosarcoma cell line. 1060 50

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

Alterations in cathepsin L expression and trafficking have been associated with the progression and metastasis of several tumor entities. In the present study, we examined the effects of various cathepsin L antisense (as) phosphorothioate oligonucleotides on both the expression of cathepsin L and the invasive potential of the human osteosarcoma cell line MNNG/HOS. Seven oligonucleotides of 20-bp length each and one random control oligonucleotide were chosen to block cathepsin L expression. Northern blot analysis demonstrated a significant reduction in cathepsin L mRNA expression by the six antisense oligonucleotides at a concentration of 10 microM. Cathepsin L protein expression was reduced significantly (50-85%) by the antisense oligonucleotides, as compared with the controls. Adhesion to matrices of collagen I and matrigel was not affected. In in vitro motility and invasion assays performed in uncoated and precoated transwell chambers, the ability of cells to migrate through the filters was inhibited by 35-75% using antisense oligonucleotides. The random control did not show any inhibitory effect. These data demonstrate that in MNNG/HOS cells cathepsin L influences cellular malignancy by promoting migration and basement membrane degradation.
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PMID:Cathepsin L antisense oligonucleotides in a human osteosarcoma cell line: effects on the invasive phenotype. 1149 74

Perlecan/HSPG2 is a large, multi-domain, multifunctional heparan sulfate proteoglycan with a wide tissue distribution. With the exception of its unique domain I, each of perlecan's other four domains shares sequence similarity to other protein families including low density lipoprotein (LDL) receptor, laminin alpha chain, neural cell adhesion molecule (NCAM), immunoglobulin (Ig) superfamily members, and epidermal growth factor (EGF). Previous studies demonstrated that glycosaminoglycan-bearing perlecan domain I supports early chondrogenesis and growth factor delivery. Other sites in the core protein interact with other matrix molecules and support cell adhesion, although the peptide sequences involved remain unidentified. To identify novel functional motifs within perlecan, we used a bioinformatics approach to predict regions likely to be on the exterior of the folded protein. Unique hydrophilic sequences of about 18 amino acids were selected for testing in cell adhesion assays. A novel peptide sequence (TWSKVGGHLRPGIVQSG) from an immunoglobulin (Ig) repeat in domain IV supported rapid cell adhesion, spreading and focal adhesion kinase (FAK) activation when compared to other peptides, a randomly scrambled sequence of the domain IV peptide or a negative control protein. MG-63 human osteosarcoma cells, epithelial cells and multipotent C(3)H10T1/2 cells, but not bone marrow cells, rapidly, i.e., within 30 min, formed focal adhesions and assembled an actin cytoskeleton on domain IV peptide. Cell lines differentially adhered to the domain IV peptide, suggesting adhesion is receptor specific. Adhesion was divalent cation independent and heparin sensitive, a finding that may explain some previously poorly understood observations obtained with intact perlecan. Collectively, these studies demonstrate the feasibility of using bioinformatics-based strategies to identify novel functional motifs in matrix proteins such as perlecan.
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PMID:A novel peptide sequence in perlecan domain IV supports cell adhesion, spreading and FAK activation. 1799 86


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