TY - JOUR
T1 - Integrin α4β1 involvement in stromal cell-derived factor-1α-promoted myeloma cell transendothelial migration and adhesion
T2 - Role of cAMP and the actin cytoskeleton in adhesion
AU - Parmo-Cabañas, Marisa
AU - Bartolomé, Rubén A.
AU - Wright, Natalia
AU - Hidalgo, Andrés
AU - Drager, Angelika M.
AU - Teixidó, Joaquin
N1 - Funding Information:
This work was supported by grants FIS 01/1168 and G03/136 from Ministerio de Sanidad y Consumo, and SAF2002-00207 from Ministerio de Ciencia y Tecnologı́a.
PY - 2004/4/1
Y1 - 2004/4/1
N2 - The chemokine stromal cell-derived factor-1alpha (SDF-1α) is expressed by bone arrow (BM) stromal cells and plays key roles in cell homing to and retention into the bone marrow. In multiple myeloma, blood-borne malignant plasma cells home to the BM and accumulate in contact with stromal cells, implicating myeloma cell migration across endothelium. Myeloma cells express the SDF-1α receptor CXCR4, as well as the integrin α4ß1, which mediates their attachment to BM stroma. We show here that SDF-1α promotes transendothelial migration of purified BM myeloma cells and myeloma-derived NCI-H929 cells, involving a transient upregulation of α4ß1-dependent cell adhesion to the endothelium. Characterization of intracellular signaling pathways involved in the modulation by SDF-1α of α4ß1-mediated myeloma cell adhesion revealed that intracellular cAMP amounts associated with the activation of protein kinase A play key roles in this modulation. Furthermore, a functional link between cAMP actions on the dynamics of actin cytoskeleton, RhoA activation, and α4ß1-dependent cell adhesion in response to SDF-1α has been found. The regulation of α4ß1-mediated myeloma cell adhesion by SDF-1α could play key roles during myeloma cell homing into and trafficking inside the BM, and characterization of the molecular events involved in SDF-1α-activated modulation of this adhesion will contribute to a better understanding of mechanisms participating in cell migration.
AB - The chemokine stromal cell-derived factor-1alpha (SDF-1α) is expressed by bone arrow (BM) stromal cells and plays key roles in cell homing to and retention into the bone marrow. In multiple myeloma, blood-borne malignant plasma cells home to the BM and accumulate in contact with stromal cells, implicating myeloma cell migration across endothelium. Myeloma cells express the SDF-1α receptor CXCR4, as well as the integrin α4ß1, which mediates their attachment to BM stroma. We show here that SDF-1α promotes transendothelial migration of purified BM myeloma cells and myeloma-derived NCI-H929 cells, involving a transient upregulation of α4ß1-dependent cell adhesion to the endothelium. Characterization of intracellular signaling pathways involved in the modulation by SDF-1α of α4ß1-mediated myeloma cell adhesion revealed that intracellular cAMP amounts associated with the activation of protein kinase A play key roles in this modulation. Furthermore, a functional link between cAMP actions on the dynamics of actin cytoskeleton, RhoA activation, and α4ß1-dependent cell adhesion in response to SDF-1α has been found. The regulation of α4ß1-mediated myeloma cell adhesion by SDF-1α could play key roles during myeloma cell homing into and trafficking inside the BM, and characterization of the molecular events involved in SDF-1α-activated modulation of this adhesion will contribute to a better understanding of mechanisms participating in cell migration.
KW - Cell adhesion
KW - Cell migration
KW - Chemokines
KW - Integrins
KW - Multiple myeloma
UR - http://www.scopus.com/inward/record.url?scp=1542298999&partnerID=8YFLogxK
U2 - 10.1016/j.yexcr.2003.12.003
DO - 10.1016/j.yexcr.2003.12.003
M3 - Article
C2 - 15023543
AN - SCOPUS:1542298999
SN - 0014-4827
VL - 294
SP - 571
EP - 580
JO - Experimental Cell Research
JF - Experimental Cell Research
IS - 2
ER -