Tissue factor pathway inhibitor upregulates CXCR7 expression and enhances CXCL12-mediated migration in chronic lymphocytic leukemia.
Research article published in Scientific reports (2021)
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.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Resumen
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.
Por qué esto importa para la hirudoterapia
Este estudio examinó el papel del inhibidor de la vía del factor tisular (TFPI), un inhibidor endógeno de serina proteasas, en la migración mediada por CXCL12 de células de leucemia linfocítica crónica (LLC). Los autores hallaron concentraciones plasmáticas elevadas de TFPI en pacientes con LLC —particularmente en aquellos con enfermedad avanzada— y demostraron que el TFPI aumenta la migración transendotelial de células de LLC mediante la regulación al alza del receptor de CXCL12 CXCR7 a través de la unión a glipicano-3 y la activación de β-catenina. El estudio no tiene relevancia para el dominio de ASH: el resumen no contiene ninguna mención a sanguijuelas, hirudoterapia ni moléculas derivadas de sanguijuela. Está enfocado por completo en el papel de una proteína humana en el tráfico de células leucémicas y la señalización CXCL12/CXCR7, sin ninguna conexión demostrada con la sanguijuela terapéutica ni el secretoma de la sanguijuela.
Citación
Tissue factor pathway inhibitor upregulates CXCR7 expression and enhances CXCL12-mediated migration in chronic lymphocytic leukemia.
Cui et al. · Scientific reports, 2021
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Añadido a la biblioteca ASH: May 28, 2026 · Última actualización del sitio: 18 de junio de 2026