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Tissue factor pathway inhibitor upregulates CXCR7 expression and enhances CXCL12-mediated migration in chronic lymphocytic leukemia

The infiltration of chronic lymphocytic leukemia (CLL) cells into lymphoid organs correlates with disease severity. CXCL12 is a key chemotactic factor for the trafficking of CLL. Tissue factor pathway inhibitor (TFPI) is a serine protease inhibitor and plays a role in CXCL12-mediated hematopoietic s...

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Autores principales: Cui, Xue Yan, Tjønnfjord, Geir Erland, Kanse, Sandip M., Dahm, Anders Erik Astrup, Iversen, Nina, Myklebust, Christiane Filion, Sun, Ling, Jiang, Zhong Xing, Ueland, Thor, Campbell, James J., Ho, Mitchell, Sandset, Per Morten
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7933411/
https://www.ncbi.nlm.nih.gov/pubmed/33664415
http://dx.doi.org/10.1038/s41598-021-84695-8
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author Cui, Xue Yan
Tjønnfjord, Geir Erland
Kanse, Sandip M.
Dahm, Anders Erik Astrup
Iversen, Nina
Myklebust, Christiane Filion
Sun, Ling
Jiang, Zhong Xing
Ueland, Thor
Campbell, James J.
Ho, Mitchell
Sandset, Per Morten
author_facet Cui, Xue Yan
Tjønnfjord, Geir Erland
Kanse, Sandip M.
Dahm, Anders Erik Astrup
Iversen, Nina
Myklebust, Christiane Filion
Sun, Ling
Jiang, Zhong Xing
Ueland, Thor
Campbell, James J.
Ho, Mitchell
Sandset, Per Morten
author_sort Cui, Xue Yan
collection PubMed
description The infiltration of chronic lymphocytic leukemia (CLL) cells into lymphoid organs correlates with disease severity. CXCL12 is a key chemotactic factor for the trafficking of CLL. Tissue factor pathway inhibitor (TFPI) is a serine protease inhibitor and plays a role in CXCL12-mediated hematopoietic stem cell homing. We aim to explore the role of TFPI in CXCL12-mediated migration of CLL cells. In this study, plasma TFPI concentrations were measured by ELISA. CLL cells were isolated from patients and used for trans-endothelial migration (TEM) assays. Quantitative RT-PCR and Western blotting were used to detect the expression of CXCR7, CXCR4 and β-catenin. Immunofluorescence and co-immunoprecipitation was used to detect the binding of TFPI and glypican-3 (GPC3). We found that plasma TFPI levels in CLL patients were higher than in healthy controls, particularly in the patients with advanced disease. TFPI enhanced CXCL12-mediated TEM of CLL cells by increasing the expression of the CXCL12 receptor CXCR7, but not of the CXCL12 receptor CXCR4. The effect of TFPI on TEM was abolished by the CXCR7 inhibitor, CCX771, while the CXCR4 inhibitor AMD3100 strongly increased TEM. TFPI co-localized with GPC3 on the cell surface. An antibody to GPC3, HS20, decreased CXCR7 expression and abolished the effect of TFPI on TEM. TFPI activated β-catenin and the Wnt/β-catenin inhibitor IWP4 repressed the effect of TFPI on CXCR7 expression and TEM. We conclude that TFPI may contribute to organ infiltration in CLL patients.
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spelling pubmed-79334112021-03-08 Tissue factor pathway inhibitor upregulates CXCR7 expression and enhances CXCL12-mediated migration in chronic lymphocytic leukemia Cui, Xue Yan Tjønnfjord, Geir Erland Kanse, Sandip M. Dahm, Anders Erik Astrup Iversen, Nina Myklebust, Christiane Filion Sun, Ling Jiang, Zhong Xing Ueland, Thor Campbell, James J. Ho, Mitchell Sandset, Per Morten Sci Rep Article The infiltration of chronic lymphocytic leukemia (CLL) cells into lymphoid organs correlates with disease severity. CXCL12 is a key chemotactic factor for the trafficking of CLL. Tissue factor pathway inhibitor (TFPI) is a serine protease inhibitor and plays a role in CXCL12-mediated hematopoietic stem cell homing. We aim to explore the role of TFPI in CXCL12-mediated migration of CLL cells. In this study, plasma TFPI concentrations were measured by ELISA. CLL cells were isolated from patients and used for trans-endothelial migration (TEM) assays. Quantitative RT-PCR and Western blotting were used to detect the expression of CXCR7, CXCR4 and β-catenin. Immunofluorescence and co-immunoprecipitation was used to detect the binding of TFPI and glypican-3 (GPC3). We found that plasma TFPI levels in CLL patients were higher than in healthy controls, particularly in the patients with advanced disease. TFPI enhanced CXCL12-mediated TEM of CLL cells by increasing the expression of the CXCL12 receptor CXCR7, but not of the CXCL12 receptor CXCR4. The effect of TFPI on TEM was abolished by the CXCR7 inhibitor, CCX771, while the CXCR4 inhibitor AMD3100 strongly increased TEM. TFPI co-localized with GPC3 on the cell surface. An antibody to GPC3, HS20, decreased CXCR7 expression and abolished the effect of TFPI on TEM. TFPI activated β-catenin and the Wnt/β-catenin inhibitor IWP4 repressed the effect of TFPI on CXCR7 expression and TEM. We conclude that TFPI may contribute to organ infiltration in CLL patients. Nature Publishing Group UK 2021-03-04 /pmc/articles/PMC7933411/ /pubmed/33664415 http://dx.doi.org/10.1038/s41598-021-84695-8 Text en © The Author(s) 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Cui, Xue Yan
Tjønnfjord, Geir Erland
Kanse, Sandip M.
Dahm, Anders Erik Astrup
Iversen, Nina
Myklebust, Christiane Filion
Sun, Ling
Jiang, Zhong Xing
Ueland, Thor
Campbell, James J.
Ho, Mitchell
Sandset, Per Morten
Tissue factor pathway inhibitor upregulates CXCR7 expression and enhances CXCL12-mediated migration in chronic lymphocytic leukemia
title Tissue factor pathway inhibitor upregulates CXCR7 expression and enhances CXCL12-mediated migration in chronic lymphocytic leukemia
title_full Tissue factor pathway inhibitor upregulates CXCR7 expression and enhances CXCL12-mediated migration in chronic lymphocytic leukemia
title_fullStr Tissue factor pathway inhibitor upregulates CXCR7 expression and enhances CXCL12-mediated migration in chronic lymphocytic leukemia
title_full_unstemmed Tissue factor pathway inhibitor upregulates CXCR7 expression and enhances CXCL12-mediated migration in chronic lymphocytic leukemia
title_short Tissue factor pathway inhibitor upregulates CXCR7 expression and enhances CXCL12-mediated migration in chronic lymphocytic leukemia
title_sort tissue factor pathway inhibitor upregulates cxcr7 expression and enhances cxcl12-mediated migration in chronic lymphocytic leukemia
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7933411/
https://www.ncbi.nlm.nih.gov/pubmed/33664415
http://dx.doi.org/10.1038/s41598-021-84695-8
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