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Plasma Fibronectin Promotes Tumor Cell Survival and Invasion through Regulation of Tie2

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 (TN...

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Autores principales: Knowles, Lynn M., Malik, Gunjan, Pilch, Jan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3701808/
https://www.ncbi.nlm.nih.gov/pubmed/23833683
http://dx.doi.org/10.7150/jca.6545
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author Knowles, Lynn M.
Malik, Gunjan
Pilch, Jan
author_facet Knowles, Lynn M.
Malik, Gunjan
Pilch, Jan
author_sort Knowles, Lynn M.
collection PubMed
description 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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spelling pubmed-37018082013-07-05 Plasma Fibronectin Promotes Tumor Cell Survival and Invasion through Regulation of Tie2 Knowles, Lynn M. Malik, Gunjan Pilch, Jan J Cancer Research Paper 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. Ivyspring International Publisher 2013-06-21 /pmc/articles/PMC3701808/ /pubmed/23833683 http://dx.doi.org/10.7150/jca.6545 Text en © Ivyspring International Publisher. This is an open-access article distributed under the terms of the Creative Commons License (http://creativecommons.org/licenses/by-nc-nd/3.0/). Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited.
spellingShingle Research Paper
Knowles, Lynn M.
Malik, Gunjan
Pilch, Jan
Plasma Fibronectin Promotes Tumor Cell Survival and Invasion through Regulation of Tie2
title Plasma Fibronectin Promotes Tumor Cell Survival and Invasion through Regulation of Tie2
title_full Plasma Fibronectin Promotes Tumor Cell Survival and Invasion through Regulation of Tie2
title_fullStr Plasma Fibronectin Promotes Tumor Cell Survival and Invasion through Regulation of Tie2
title_full_unstemmed Plasma Fibronectin Promotes Tumor Cell Survival and Invasion through Regulation of Tie2
title_short Plasma Fibronectin Promotes Tumor Cell Survival and Invasion through Regulation of Tie2
title_sort plasma fibronectin promotes tumor cell survival and invasion through regulation of tie2
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3701808/
https://www.ncbi.nlm.nih.gov/pubmed/23833683
http://dx.doi.org/10.7150/jca.6545
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