The Experts below are selected from a list of 93 Experts worldwide ranked by ideXlab platform
Jan Pilch - One of the best experts on this subject based on the ideXlab platform.
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Plasma Fibronectin promotes tumor cell survival and invasion through regulation of tie2
Journal of Cancer, 2013Co-Authors: Lynn M Knowles, Gunjan Malik, Jan PilchAbstract:Our previous research has shown that Plasma Fibronectin promotes lung metastasis by facilitating tumor cell invasion in clotted Plasma. To evaluate the role of clotted Plasma for tumor cell survival, we treated B16F1 cells embedded in a 3-dimensional matrix of fibrin with tumor necrosis factor α (TNFα), a cytokine with anti-tumor activity. Under these conditions, TNFα caused significant cytotoxicity, which was prevented when we added Plasma Fibronectin to the fibrin clot. Fibronectin-mediated TNFα resistance was dependent on PI3-kinase, which also mediated the pro-adhesive and pro-invasive effects of Plasma Fibronectin on tumor cells. To further investigate the role of Plasma Fibronectin in tumor cell signaling, we performed a gene array that showed specific upregulation of Tie2 in B16F1 cells embedded in fibrin-Fibronectin compared to fibrin. Importantly, inhibition of Tie2 resulted in decreased tumor cell invasion, reduced colony formation and increased tumor cell death in response to TNFα. Together, our findings indicate that Plasma Fibronectin induces tumor cell invasion and protects tumor cells from the cytotoxic effects of inflammatory mediators through up-regulation of Tie2.
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Plasma Fibronectin promotes lung metastasis by contributions to fibrin clots and tumor cell invasion
Cancer Research, 2010Co-Authors: Gunjan Malik, Lynn M Knowles, Rajiv Dhir, Shuting Yang, Erkki Ruoslahti, Jan PilchAbstract:The attachment of circulating tumor cells to the blood vessels of distant organs is an important step in metastasis. We show here that experimental lung metastasis by two cell lines, B16F1 melanoma and 3LL lung carcinoma, is greatly reduced in transgenic mice that lack Plasma Fibronectin. This multifunctional adhesive glycoprotein becomes cross-linked to fibrin during clotting. Here, we report that eliminating Plasma Fibronectin from the blood circulation reverses the prometastatic effects of blood clotting and tumor cell integrin αvβ3. In vitro studies showed that fibrin-Fibronectin complexes, but not purified fibrin, supported tumor cell attachment and invasion. These functions correlate with the ability of fibrin-Fibronectin complexes to induce the activation of integrin αvβ3. Our findings reveal an important contribution of Plasma Fibronectin in lung metastasis. Furthermore, they suggest that the previously noted effects of blood clotting on lung metastasis might be mediated in part by a Fibronectin-αvβ3 integrin axis, in which Plasma Fibronectin has to be incorporated into the blood clot. Cancer Res; 70(11); 4327–34. ©2010 AACR.
John H. Griffin - One of the best experts on this subject based on the ideXlab platform.
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Elevated Plasma Fibronectin levels associated with venous thromboembolism
2008Co-Authors: Natalie M. Pecheniuk, Darlene J. Elias, Hiroshi Deguchi, Patricia M. Averell, John H. GriffinAbstract:Elevated Plasma Fibronectin levels occur in various clinical states including arterial disease. Increasing evidence suggests that atherothrombosis and venous thromboembolism (VTE) share common risk factors. To assess the hypothesis that high Plasma Fibronectin levels are associated with VTE, we compared Plasma Fibronectin levels in the Scripps Venous Thrombosis Registry for 113 VTE cases vs. age and sex matched controls. VTE cases had significantly higher mean Fibronectin concentration compared to controls (127% vs. 103%, p 90% of the control values, the odds ratio (OR) for association of VTE for Fibronectin Plasma levels above the 90th percentile were 9.37 (95% CI 2.73-32.2; p
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Elevated Plasma Fibronectin levels associated with venous thromboembolism.
Thrombosis and haemostasis, 2008Co-Authors: Natalie M. Pecheniuk, Darlene J. Elias, Hiroshi Deguchi, Patricia M. Averell, John H. GriffinAbstract:Elevated Plasma Fibronectin levels occur in various clinical states including arterial disease. Increasing evidence suggests that atherothrombosis and venous thromboembolism (VTE) share common risk factors. To assess the hypothesis that high Plasma Fibronectin levels are associated with VTE, we compared Plasma Fibronectin levels in the Scripps Venous Thrombosis Registry for 113 VTE cases vs. age and sex matched controls. VTE cases had significantly higher mean Fibronectin concentration compared to controls (127% vs. 103%, p 90% of the control values, the odds ratio (OR) for association of VTE for Fibronectin Plasma levels above the 90(th) percentile were 9.37 (95% CI 2.73-32.2; p < 0.001) and this OR remained significant after adjustment for sex, age, body mass index (BMI), factor V Leiden and prothrombin nt20210A (OR 7.60, 95% CI 2.14-27.0; p = 0.002). In particular, the OR was statistically significant for idiopathic VTE before and after these statistical adjustments. For the total male cohort, the OR was significant before and after statistical adjustments and was not significant for the total female cohort. In summary, our results suggest that elevated Plasma Fibronectin levels are associated with VTE especially in males, and extend the potential association between biomarkers and risk factors for arterial atherothrombosis and VTE.
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elevated Plasma Fibronectin levels associated with venous thromboembolism
Institute of Health and Biomedical Innovation, 2008Co-Authors: Natalie M. Pecheniuk, Darlene J. Elias, Hiroshi Deguchi, Patricia M. Averell, John H. GriffinAbstract:Elevated Plasma Fibronectin levels occur in various clinical states including arterial disease. Increasing evidence suggests that atherothrombosis and venous thromboembolism (VTE) share common risk factors. To assess the hypothesis that high Plasma Fibronectin levels are associated with VTE, we compared Plasma Fibronectin levels in the Scripps Venous Thrombosis Registry for 113 VTE cases vs. age and sex matched controls. VTE cases had significantly higher mean Fibronectin concentration compared to controls (127% vs. 103%, p 90% of the control values, the odds ratio (OR) for association of VTE for Fibronectin Plasma levels above the 90th percentile were 9.37 (95% CI 2.73-32.2; p<0.001) and this OR remained significant after adjustment for sex, age, body mass index (BMI), factor V Leiden and prothrombin nt20210A (OR 7.60, 95% CI 2.14-27.0; p=0.002). In particular, the OR was statistically significant for idiopathic VTE before and after these statistical adjustments. For the total male cohort, the OR was significant before and after statistical adjustments and was not significant for the total female cohort. In summary, our results suggest that elevated Plasma Fibronectin levels are associated with VTE especially in males, and extend the potential association between biomarkers and risk factors for arterial atherothrombosis and VTE. © 2008 Schattauer GmbH.
Gunjan Malik - One of the best experts on this subject based on the ideXlab platform.
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Plasma Fibronectin promotes tumor cell survival and invasion through regulation of tie2
Journal of Cancer, 2013Co-Authors: Lynn M Knowles, Gunjan Malik, Jan PilchAbstract:Our previous research has shown that Plasma Fibronectin promotes lung metastasis by facilitating tumor cell invasion in clotted Plasma. To evaluate the role of clotted Plasma for tumor cell survival, we treated B16F1 cells embedded in a 3-dimensional matrix of fibrin with tumor necrosis factor α (TNFα), a cytokine with anti-tumor activity. Under these conditions, TNFα caused significant cytotoxicity, which was prevented when we added Plasma Fibronectin to the fibrin clot. Fibronectin-mediated TNFα resistance was dependent on PI3-kinase, which also mediated the pro-adhesive and pro-invasive effects of Plasma Fibronectin on tumor cells. To further investigate the role of Plasma Fibronectin in tumor cell signaling, we performed a gene array that showed specific upregulation of Tie2 in B16F1 cells embedded in fibrin-Fibronectin compared to fibrin. Importantly, inhibition of Tie2 resulted in decreased tumor cell invasion, reduced colony formation and increased tumor cell death in response to TNFα. Together, our findings indicate that Plasma Fibronectin induces tumor cell invasion and protects tumor cells from the cytotoxic effects of inflammatory mediators through up-regulation of Tie2.
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Plasma Fibronectin promotes lung metastasis by contributions to fibrin clots and tumor cell invasion
Cancer Research, 2010Co-Authors: Gunjan Malik, Lynn M Knowles, Rajiv Dhir, Shuting Yang, Erkki Ruoslahti, Jan PilchAbstract:The attachment of circulating tumor cells to the blood vessels of distant organs is an important step in metastasis. We show here that experimental lung metastasis by two cell lines, B16F1 melanoma and 3LL lung carcinoma, is greatly reduced in transgenic mice that lack Plasma Fibronectin. This multifunctional adhesive glycoprotein becomes cross-linked to fibrin during clotting. Here, we report that eliminating Plasma Fibronectin from the blood circulation reverses the prometastatic effects of blood clotting and tumor cell integrin αvβ3. In vitro studies showed that fibrin-Fibronectin complexes, but not purified fibrin, supported tumor cell attachment and invasion. These functions correlate with the ability of fibrin-Fibronectin complexes to induce the activation of integrin αvβ3. Our findings reveal an important contribution of Plasma Fibronectin in lung metastasis. Furthermore, they suggest that the previously noted effects of blood clotting on lung metastasis might be mediated in part by a Fibronectin-αvβ3 integrin axis, in which Plasma Fibronectin has to be incorporated into the blood clot. Cancer Res; 70(11); 4327–34. ©2010 AACR.
Deane F. Mosher - One of the best experts on this subject based on the ideXlab platform.
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dynamic structure of Plasma Fibronectin
Critical Reviews in Biochemistry and Molecular Biology, 2016Co-Authors: Lisa M Maurer, Deane F. MosherAbstract:Fibronectin is a large vertebrate glycoprotein that is found in soluble and insoluble forms and involved in diverse processes. Protomeric Fibronectin is a dimer of subunits, each of which comprises 29-31 modules - 12 type I, two type II and 15-17 type III. Plasma Fibronectin is secreted by hepatocytes and circulates in a compact conformation before it binds to cell surfaces, converts to an extended conformation and is assembled into Fibronectin fibrils. Here we review biophysical and structural studies that have shed light on how Plasma Fibronectin transitions from the compact to the extended conformation. The three types of modules each have a well-organized secondary and tertiary structure as defined by NMR and crystallography and have been likened to "beads on a string". There are flexible sequences in the N-terminal tail, between the fifth and sixth type I modules, between the first two and last two of the type III modules, and at the C-terminus. Several specific module-module interactions have been identified that likely maintain the compact quaternary structure of circulating Fibronectin. The quaternary structure is perturbed in response to binding events, including binding of Fibronectin to the surface of vertebrate cells for fibril assembly and to bacterial adhesins.
Lynn M Knowles - One of the best experts on this subject based on the ideXlab platform.
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Plasma Fibronectin promotes tumor cell survival and invasion through regulation of tie2
Journal of Cancer, 2013Co-Authors: Lynn M Knowles, Gunjan Malik, Jan PilchAbstract:Our previous research has shown that Plasma Fibronectin promotes lung metastasis by facilitating tumor cell invasion in clotted Plasma. To evaluate the role of clotted Plasma for tumor cell survival, we treated B16F1 cells embedded in a 3-dimensional matrix of fibrin with tumor necrosis factor α (TNFα), a cytokine with anti-tumor activity. Under these conditions, TNFα caused significant cytotoxicity, which was prevented when we added Plasma Fibronectin to the fibrin clot. Fibronectin-mediated TNFα resistance was dependent on PI3-kinase, which also mediated the pro-adhesive and pro-invasive effects of Plasma Fibronectin on tumor cells. To further investigate the role of Plasma Fibronectin in tumor cell signaling, we performed a gene array that showed specific upregulation of Tie2 in B16F1 cells embedded in fibrin-Fibronectin compared to fibrin. Importantly, inhibition of Tie2 resulted in decreased tumor cell invasion, reduced colony formation and increased tumor cell death in response to TNFα. Together, our findings indicate that Plasma Fibronectin induces tumor cell invasion and protects tumor cells from the cytotoxic effects of inflammatory mediators through up-regulation of Tie2.
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Plasma Fibronectin promotes lung metastasis by contributions to fibrin clots and tumor cell invasion
Cancer Research, 2010Co-Authors: Gunjan Malik, Lynn M Knowles, Rajiv Dhir, Shuting Yang, Erkki Ruoslahti, Jan PilchAbstract:The attachment of circulating tumor cells to the blood vessels of distant organs is an important step in metastasis. We show here that experimental lung metastasis by two cell lines, B16F1 melanoma and 3LL lung carcinoma, is greatly reduced in transgenic mice that lack Plasma Fibronectin. This multifunctional adhesive glycoprotein becomes cross-linked to fibrin during clotting. Here, we report that eliminating Plasma Fibronectin from the blood circulation reverses the prometastatic effects of blood clotting and tumor cell integrin αvβ3. In vitro studies showed that fibrin-Fibronectin complexes, but not purified fibrin, supported tumor cell attachment and invasion. These functions correlate with the ability of fibrin-Fibronectin complexes to induce the activation of integrin αvβ3. Our findings reveal an important contribution of Plasma Fibronectin in lung metastasis. Furthermore, they suggest that the previously noted effects of blood clotting on lung metastasis might be mediated in part by a Fibronectin-αvβ3 integrin axis, in which Plasma Fibronectin has to be incorporated into the blood clot. Cancer Res; 70(11); 4327–34. ©2010 AACR.