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

Abstract 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 hemato...

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Autores principales:	Xue Yan Cui, Geir Erland Tjønnfjord, Sandip M. Kanse, Anders Erik Astrup Dahm, Nina Iversen, Christiane Filion Myklebust, Ling Sun, Zhong Xing Jiang, Thor Ueland, James J. Campbell, Mitchell Ho, Per Morten Sandset
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ce0caf0c3fe64d058cc6da40b15f9c56
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spelling	oai:doaj.org-article:ce0caf0c3fe64d058cc6da40b15f9c562021-12-02T13:30:11ZTissue factor pathway inhibitor upregulates CXCR7 expression and enhances CXCL12-mediated migration in chronic lymphocytic leukemia10.1038/s41598-021-84695-82045-2322https://doaj.org/article/ce0caf0c3fe64d058cc6da40b15f9c562021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-84695-8https://doaj.org/toc/2045-2322Abstract 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.Xue Yan CuiGeir Erland TjønnfjordSandip M. KanseAnders Erik Astrup DahmNina IversenChristiane Filion MyklebustLing SunZhong Xing JiangThor UelandJames J. CampbellMitchell HoPer Morten SandsetNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Xue Yan Cui Geir Erland Tjønnfjord Sandip M. Kanse Anders Erik Astrup Dahm Nina Iversen Christiane Filion Myklebust Ling Sun Zhong Xing Jiang Thor Ueland James J. Campbell Mitchell Ho Per Morten Sandset Tissue factor pathway inhibitor upregulates CXCR7 expression and enhances CXCL12-mediated migration in chronic lymphocytic leukemia
description	Abstract 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.
format	article
author	Xue Yan Cui Geir Erland Tjønnfjord Sandip M. Kanse Anders Erik Astrup Dahm Nina Iversen Christiane Filion Myklebust Ling Sun Zhong Xing Jiang Thor Ueland James J. Campbell Mitchell Ho Per Morten Sandset
author_facet	Xue Yan Cui Geir Erland Tjønnfjord Sandip M. Kanse Anders Erik Astrup Dahm Nina Iversen Christiane Filion Myklebust Ling Sun Zhong Xing Jiang Thor Ueland James J. Campbell Mitchell Ho Per Morten Sandset
author_sort	Xue Yan Cui
title	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_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_sort	tissue factor pathway inhibitor upregulates cxcr7 expression and enhances cxcl12-mediated migration in chronic lymphocytic leukemia
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/ce0caf0c3fe64d058cc6da40b15f9c56
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Tissue factor pathway inhibitor upregulates CXCR7 expression and enhances CXCL12-mediated migration in chronic lymphocytic leukemia

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