Sanz-Rodríguez F, Hidalgo A, Teixidó J
Department of Immunology, Centro de Investigaciones Biológicas, Madrid, Spain.
Blood. 2001 Jan 15;97(2):346-51. doi: 10.1182/blood.v97.2.346.
The chemokine stromal cell-derived factor-1alpha (SDF-1alpha) and its G-protein-linked receptor CXCR4 are involved in hematopoietic progenitor cell and lymphocyte migration. The integrin VLA-4 is a cell adhesion receptor for CS-1/fibronectin and VCAM-1 and constitutes one of the main adhesion receptors mediating myeloma cell adhesion to bone marrow (BM) stroma in multiple myeloma (MM). It is shown here that MM CD38(hi)CD45RA(-) BM cells and myeloma-derived cell lines expressed CXCR4 and displayed a moderate chemotactic response to SDF-1alpha. Because cell migration in response to SDF-1alpha might require a dynamic regulation of integrin function, it was investigated whether SDF-1alpha can modulate VLA-4 function on myeloma cells. SDF-1alpha rapidly and transiently up-regulated VLA-4-mediated myeloma cell adhesion to both CS-1/fibronectin and VCAM-1, which was inhibited by pertussis toxin and cytochalasin D, indicating the involvement of G(i) protein downstream signaling and an intact cytoskeleton. Modulation of VLA-4-dependent myeloma cell adhesion by SDF-1alpha could contribute to the trafficking and localization of these cells in the BM microenvironment.
趋化因子基质细胞衍生因子-1α（SDF-1α）及其G蛋白偶联受体CXCR4参与造血祖细胞和淋巴细胞的迁移。整合素VLA-4是CS-1/纤连蛋白和血管细胞黏附分子-1（VCAM-1）的细胞黏附受体，是介导多发性骨髓瘤（MM）中骨髓瘤细胞与骨髓（BM）基质黏附的主要黏附受体之一。本文显示，MM CD38(hi)CD45RA(-) BM细胞和骨髓瘤衍生细胞系表达CXCR4，并对SDF-1α表现出适度的趋化反应。由于细胞对SDF-1α的迁移可能需要整合素功能的动态调节，因此研究了SDF-1α是否能调节骨髓瘤细胞上的VLA-4功能。SDF-1α迅速且短暂地上调VLA-4介导的骨髓瘤细胞对CS-1/纤连蛋白和VCAM-1的黏附，百日咳毒素和细胞松弛素D可抑制这种黏附，表明G(i)蛋白下游信号传导和完整的细胞骨架参与其中。SDF-1α对VLA-4依赖性骨髓瘤细胞黏附的调节可能有助于这些细胞在BM微环境中的运输和定位。
