SDF-1/CXCR4 and VLA-4 interaction regulates homing in Waldenstrom macroglobulinemia
- 1 July 2008
- journal article
- Published by American Society of Hematology in Blood
- Vol. 112 (1), 150-158
- https://doi.org/10.1182/blood-2007-12-129395
Abstract
Waldenstrom macroglobulinemia (WM) is characterized by widespread involvement of the bone marrow at the time of diagnosis, implying continuous homing of WM cells into the marrow. The mechanisms by which trafficking of the malignant cells into the bone marrow has not been previously elucidated. In this study, we show that WM cells express high levels of chemokine and adhesion receptors, including CXCR4 and VLA-4. We showed that CXCR4 was essential for the migration and trans-endothelial migration of WM cells under static and dynamic shear flow conditions, with significant inhibition of migration using CXCR4 knockdown or the CXCR4 inhibitor AMD3100. Similarly, CXCR4 or VLA-4 inhibition led to significant inhibition of adhesion to fibronectin, stromal cells, and endothelial cells. Decreased adhesion of WM cells to stromal cells by AMD3100 led to increased sensitivity of these cells to cytotoxicity by bortezomib. To further investigate the mechanisms of CXCR4-dependent adhesion, we showed that CXCR4 and VLA-4 directly interact in response to SDF-1, we further investigated downstream signaling pathways regulating migration and adhesion in WM. Together, these studies demonstrate that the CXCR4/SDF-1 axis interacts with VLA-4 in regulating migration and adhesion of WM cells in the bone marrow microenvironment.This publication has 29 references indexed in Scilit:
- The Akt pathway regulates survival and homing in Waldenstrom macroglobulinemiaBlood, 2007
- Establishment of BCWM.1 cell line for Waldenström's macroglobulinemia with productive in vivo engraftment in SCID-hu miceExperimental Hematology, 2007
- Waldenström macroglobulinemiaBlood, 2007
- Mechanisms of regulation of CXCR4/SDF-1 (CXCL12)–dependent migration and homing in multiple myelomaBlood, 2006
- Shear flow–dependent integration of apical and subendothelial chemokines in T-cell transmigration: implications for locomotion and the multistep paradigmBlood, 2006
- Integrin signalling during tumour progressionNature Reviews Molecular Cell Biology, 2004
- Chemokines in neoplastic progressionSeminars in Cancer Biology, 2004
- Integrin α4β1 involvement in stromal cell-derived factor-1α-promoted myeloma cell transendothelial migration and adhesion: role of cAMP and the actin cytoskeleton in adhesionExperimental Cell Research, 2004
- L-selectin stimulation enhances functional expression of surface CXCR4 in lymphocytes: implications for cellular activation during adhesion and migrationBlood, 2003
- Lymphocyte Homing and HomeostasisScience, 1996