An impaired transendothelial migration potential of chronic lymphocytic leukemia (CLL) cells can be linked to ephrin-A4 expression
| Autor: | Agustín G. Zapata, Jaime Zuloaga, Luis Miguel Alonso-Colmenar, Mónica Ballesteros, Eva M. Trinidad |
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| Rok vydání: | 2009 |
| Předmět: |
CD31
Endothelium Chronic lymphocytic leukemia Immunology Intercellular Adhesion Molecule-1 Fluorescent Antibody Technique Vascular Cell Adhesion Molecule-1 Biology Biochemistry hemic and lymphatic diseases medicine Cell Adhesion Humans Microscopy Confocal Cell adhesion molecule Reverse Transcriptase Polymerase Chain Reaction Receptor EphA2 Cell migration Cell Biology Hematology medicine.disease Flow Cytometry Leukemia Lymphocytic Chronic B-Cell Ephrin-A4 Chemotaxis Leukocyte medicine.anatomical_structure Cancer research Chemokine CCL19 Tumor necrosis factor alpha Human umbilical vein endothelial cell |
| Zdroj: | Blood. 114(24) |
| ISSN: | 1528-0020 |
| Popis: | Chronic lymphocytic leukemia (CLL) cell migration into lymphoid tissues is an important aspect of the pathobiology of this disease. Here, we investigated the role of ephrin-A4 (EFNA4) in the transendothelial migration (TEM) capacity of CLL and normal B cells through interacting with endothelial EphA2 (erythropoietin-producing hepatocellular carcinoma). CLL cells showed a remarkable impairment in the adhesion to and transmigration through human umbilical vein endothelial cell (HUVEC) monolayers, correlating with their higher EFNA4 expression. In vitro, TEM was mediated by EFNA4 binding to endothelial EphA2 receptor, which is highly expressed in tumor necrosis factor-α–activated HUVECs as well as in the CD31+ endothelial cells of human lymph nodes. The pretreatment of CLL cells with EphA2 homodimers further impaired their adhesion to and transmigration through HUVEC monolayers, whereas pretreatment of HUVECs with EFNA4 homodimers improved those phenomena in both CLL and normal B cells, suggesting that EFNA4 signaling negatively contributed to TEM. In fact, EFNA4 signaling into CLL cells significantly reduced their adhesion to intercellular adhesion molecule 1, vascular cell adhesion molecule 1, and several extracellular matrix molecules and impaired CCL-19–mediated TEM and chemotaxis. Our results suggest that EFNA4-EphA2 interactions are involved in CLL cell trafficking between blood and the tissues and therefore may become a therapeutic target in the future. |
| Databáze: | OpenAIRE |
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