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Evidence that vitronectin is a potent migration-enhancing factor for cancer cells chaperoned by fibrinogen: a novel view of the metastasis of cancer cells to low-fibrinogen lymphatics and body cavities
Diluted (1%) plasma induces migration of malignant cell lines much more strongly than potent pro-metastatic factors. To characterize the factor(s) present in diluted plasma responsible for this phenomenon we performed i) heat inactivation, ii) dialysis, iii) proteinase K treatment, and iv) molecular...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5342518/ https://www.ncbi.nlm.nih.gov/pubmed/27634880 http://dx.doi.org/10.18632/oncotarget.12003 |
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author | Schneider, Gabriela Bryndza, Ewa Poniewierska-Baran, Agata Serwin, Karol Suszynska, Malwina Sellers, Zachariah P. Merchant, Michael L. Kaliappan, Alagammai Ratajczak, Janina Kucia, Magda Garbett, Nichola C. Ratajczak, Mariusz Z. |
author_facet | Schneider, Gabriela Bryndza, Ewa Poniewierska-Baran, Agata Serwin, Karol Suszynska, Malwina Sellers, Zachariah P. Merchant, Michael L. Kaliappan, Alagammai Ratajczak, Janina Kucia, Magda Garbett, Nichola C. Ratajczak, Mariusz Z. |
author_sort | Schneider, Gabriela |
collection | PubMed |
description | Diluted (1%) plasma induces migration of malignant cell lines much more strongly than potent pro-metastatic factors. To characterize the factor(s) present in diluted plasma responsible for this phenomenon we performed i) heat inactivation, ii) dialysis, iii) proteinase K treatment, and iv) molecular size filtration studies. We found that this remarkable pro-migratory activity of diluted normal plasma is associated with a ~50–100-kD protein that interacts with G(αI) protein-coupled receptors and activates p42/44 MAPK and AKT signaling in target cells. Since this pro-migratory activity of 1% plasma decreases at higher plasma concentrations (> 20%), but is retained in serum, we hypothesized that fibrinogen may be involved as a chaperone of the protein(s). To identify the pro-migratory protein(s) present in diluted plasma and fibrinogen-depleted serum, we performed gel filtration and hydrophobic interaction chromatography followed by mass spectrometry analysis. We identified several putative protein candidates that were further tested in in vitro experiments. We found that this pro-migratory factor chaperoned by fibrinogen is vitronectin, which activates uPAR, and that this effect can be inhibited by fibrinogen. These results provide a novel mechanism for the metastasis of cancer cells to lymphatics and body cavities, in which the concentration of fibrinogen is low, and thus suggests that free vitronectin stimulates migration of tumor cells. |
format | Online Article Text |
id | pubmed-5342518 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-53425182017-03-24 Evidence that vitronectin is a potent migration-enhancing factor for cancer cells chaperoned by fibrinogen: a novel view of the metastasis of cancer cells to low-fibrinogen lymphatics and body cavities Schneider, Gabriela Bryndza, Ewa Poniewierska-Baran, Agata Serwin, Karol Suszynska, Malwina Sellers, Zachariah P. Merchant, Michael L. Kaliappan, Alagammai Ratajczak, Janina Kucia, Magda Garbett, Nichola C. Ratajczak, Mariusz Z. Oncotarget Research Paper Diluted (1%) plasma induces migration of malignant cell lines much more strongly than potent pro-metastatic factors. To characterize the factor(s) present in diluted plasma responsible for this phenomenon we performed i) heat inactivation, ii) dialysis, iii) proteinase K treatment, and iv) molecular size filtration studies. We found that this remarkable pro-migratory activity of diluted normal plasma is associated with a ~50–100-kD protein that interacts with G(αI) protein-coupled receptors and activates p42/44 MAPK and AKT signaling in target cells. Since this pro-migratory activity of 1% plasma decreases at higher plasma concentrations (> 20%), but is retained in serum, we hypothesized that fibrinogen may be involved as a chaperone of the protein(s). To identify the pro-migratory protein(s) present in diluted plasma and fibrinogen-depleted serum, we performed gel filtration and hydrophobic interaction chromatography followed by mass spectrometry analysis. We identified several putative protein candidates that were further tested in in vitro experiments. We found that this pro-migratory factor chaperoned by fibrinogen is vitronectin, which activates uPAR, and that this effect can be inhibited by fibrinogen. These results provide a novel mechanism for the metastasis of cancer cells to lymphatics and body cavities, in which the concentration of fibrinogen is low, and thus suggests that free vitronectin stimulates migration of tumor cells. Impact Journals LLC 2016-09-13 /pmc/articles/PMC5342518/ /pubmed/27634880 http://dx.doi.org/10.18632/oncotarget.12003 Text en Copyright: © 2016 Schneider et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Schneider, Gabriela Bryndza, Ewa Poniewierska-Baran, Agata Serwin, Karol Suszynska, Malwina Sellers, Zachariah P. Merchant, Michael L. Kaliappan, Alagammai Ratajczak, Janina Kucia, Magda Garbett, Nichola C. Ratajczak, Mariusz Z. Evidence that vitronectin is a potent migration-enhancing factor for cancer cells chaperoned by fibrinogen: a novel view of the metastasis of cancer cells to low-fibrinogen lymphatics and body cavities |
title | Evidence that vitronectin is a potent migration-enhancing factor for cancer cells chaperoned by fibrinogen: a novel view of the metastasis of cancer cells to low-fibrinogen lymphatics and body cavities |
title_full | Evidence that vitronectin is a potent migration-enhancing factor for cancer cells chaperoned by fibrinogen: a novel view of the metastasis of cancer cells to low-fibrinogen lymphatics and body cavities |
title_fullStr | Evidence that vitronectin is a potent migration-enhancing factor for cancer cells chaperoned by fibrinogen: a novel view of the metastasis of cancer cells to low-fibrinogen lymphatics and body cavities |
title_full_unstemmed | Evidence that vitronectin is a potent migration-enhancing factor for cancer cells chaperoned by fibrinogen: a novel view of the metastasis of cancer cells to low-fibrinogen lymphatics and body cavities |
title_short | Evidence that vitronectin is a potent migration-enhancing factor for cancer cells chaperoned by fibrinogen: a novel view of the metastasis of cancer cells to low-fibrinogen lymphatics and body cavities |
title_sort | evidence that vitronectin is a potent migration-enhancing factor for cancer cells chaperoned by fibrinogen: a novel view of the metastasis of cancer cells to low-fibrinogen lymphatics and body cavities |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5342518/ https://www.ncbi.nlm.nih.gov/pubmed/27634880 http://dx.doi.org/10.18632/oncotarget.12003 |
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