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)

Approximately 20% of patients with osteosarcoma have metastatic disease in lungs or bones at diagnosis. The requirement of platelets in hematogenous dissemination of metastatic cells is now well established. Tumor cells interact with platelets and induce platelet aggregation. In this respect, metastatic potential of tumor cells correlates with their capacity to aggregate platelets in vitro. We have previously shown that thrombospondin 1 (TSP-1) is synthesized and expressed on the surface of MG-63 osteosarcoma cells and mediates platelet-osteosarcoma cell interaction. However, active sites mimicking the function of TSP-1 during platelet-osteosarcoma cell interaction are not known. In this study, a panel of antibodies directed against the N-terminal and C-terminal domains and type 1, type 2, and type 3 repeats of TSP-1 were first used to delineate the structural requirement for the binding of osteosarcoma cell surface-associated TSP-1 to platelets. A drastic inhibition of the platelet-aggregating activity of MG-63 cells was obtained in the presence of a monoclonal antibody directed against the N-terminal domain of TSP-1. Among a series of 16 synthetic peptides spanning the whole N-terminal domain of TSP-1, only synthetic peptide N12/I encompassing amino acid residues 151-164 of the N-terminal domain of TSP-1 inhibited the platelet-aggregating activity of MG-63 cells. Electron microscopy studies showed that peptide N12/I strongly inhibited platelet-osteosarcoma cell interaction. A polyclonal antibody directed against peptide N12/I specifically bound to the surface of MG-63 cells, recognized TSP-1 and drastically inhibited the platelet-aggregating activity of MG-63 cells. In addition, peptide N12/I specifically bound to fibrinogen and inhibited TSP-1/fibrinogen interaction. Overall, our results provide evidence that a fibrinogen-binding sequence located within the N-terminal domain of TSP-1 mediates the binding of osteosarcoma cell surface-associated TSP-1 to platelet-bound fibrinogen.
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PMID:Platelet-osteosarcoma cell interaction is mediated through a specific fibrinogen-binding sequence located within the N-terminal domain of thrombospondin 1. 1070 39

Savignygrin, a platelet aggregation inhibitor that possesses the RGD integrin recognition motif, has been purified from the soft tick Ornithodoros savignyi. Two isoforms with similar biological activities differ because of R52G and N60G in their amino acid sequences, indicating a recent gene duplication event. Platelet aggregation induced by ADP (IC50, 130 nm), collagen, the thrombin receptor-activating peptide, and epinephrine was inhibited, although platelets were activated and underwent a shape change. The binding of alpha-CD41 (P2) to platelets, the binding of purified alpha(IIb)beta3 to fibrinogen, and the adhesion of platelets to fibrinogen was inhibited, indicating a targeting of the fibrinogen receptor. In contrast, the adhesion of osteosarcoma cells that express the integrin alpha(v)beta3 to vitronectin or fibrinogen was not inhibited, indicating the specificity of savignygrin toward alpha(IIb)beta3. Savignygrin shows sequence identity to disagregin, a platelet aggregation inhibitor from the tick Ornithodoros moubata that lacks an RGD motif. The cysteine arrangement of savignygrin is similar to that of the bovine pancreatic trypsin inhibitor family of serine protease inhibitors. A homology model based on the structure of the tick anticoagulant peptide indicates that the RGD motif is presented on the substrate-binding loop of the canonical BPTI inhibitors. However, savignygrin did not inhibit the serine proteases fXa, plasmin, thrombin, or trypsin. This is the first report of a platelet aggregation inhibitor that presents the RGD motif using the Kunitz-BPTI protein fold.
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PMID:Savignygrin, a platelet aggregation inhibitor from the soft tick Ornithodoros savignyi, presents the RGD integrin recognition motif on the Kunitz-BPTI fold. 1193 56

Osteosarcoma is a rare cancer, which metastasizes to the lung in up to 80% of cases. Thrombin is involved in metastasis and is present in the lungs of patients with pulmonary metastases (PM). To identify its role in PM and osteosarcoma, we measured thrombin levels in the bronchoalveolar lavage fluid (BALF) of 15 patients. BALF was collected at different stages of the disease and correlated with the diagnosis of PM. We also assessed fibrinogen overexpression in the tumors. We found that 11/15 (73%) patients with high thrombin levels in the lungs developed PM within the first 12 months from primary surgery. The median thrombin concentration in the BALF of these patients increased up to 8x10(-9) M (range, 3x10(-9)M-15x10(-9)M), which represents a more than 100-fold increase compared to patients without PM (p<0.0001). Eight of 15 (53%) primary and 11/15 (73%) metastatic samples showed fibrinogen overexpression. A significant difference between high thrombin levels, fibrinogen overexpression and PM was found compared to patients without PM (p=0.00073 and p=0.025). These results show that thrombin levels are increased in the lungs of patients with primary osteosarcoma and a high risk of developing PM. They suggest that thrombin may be involved in the development of PM.
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PMID:Thrombin is present in the lungs of patients with primary extremity osteosarcoma and pulmonary metastases. 1240 70

Polyelectrolyte multilayer (PEM) coatings on biomaterials are applied to tailor adhesion, growth, and function of cells on biomedical implants. Here, biogenic and synthetic polyelectrolytes (PEL) are used for layer-by-layer assembly to study the osteogenic activity of PEM with human osteosarcoma MG-63 cells in a comparative manner. Formation of PEM is achieved with biogenic PEL fibrinogen (FBG) and poly-l-lysine (PLL) as well as biotinylated chondroitin sulfate (BCS) and avidin (AVI), while poly(allylamine hydrochloride) (PAH) and polystyrene sulfonate (PSS) represent a fully synthetic PEM used as a reference system here. Surface plasmon resonance measurements show highest layer mass for FBG/PLL and similar for PSS/PAH and BCS/AVI systems, while water contact angle and zeta potential measurements indicate larger differences for PSS/PAH and FBG/PLL but not for BCS/AVI multilayers. All PEM systems support cell adhesion and growth and promote osteogenic differentiation as well. However, FBG/PLL layers are superior regarding MG-63 cell adhesion during short-term culture, while the BCS/AVI system increases alkaline phosphatase activity in long-term culture. Particularly, a multilayer system based on affinity interaction like BCS/AVI may be useful for controlled presentation of biotinylated growth factors to promote growth and differentiation of cells for biomedical applications.
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PMID:Comparative Study of Osteogenic Activity of Multilayers Made of Synthetic and Biogenic Polyelectrolytes. 2854 77


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