Characterization of VLA-4-dependent myeloma cell adhesion to fibronectin and VCAM-1

被引:45
作者
Sanz-Rodríguez, F
Ruiz-Velasco, N
Pascual-Salcedo, D
Teixidó, J
机构
[1] Ctr Invest Biol, Dept Inmunol, E-28006 Madrid, Spain
[2] Hosp Univ La Paz, Unidad Inmunol, Madrid, Spain
关键词
myeloma; VLA-4; adhesion; fibronectin; VCAM-1;
D O I
10.1046/j.1365-2141.1999.01762.x
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The integrin VLA-4 mediates attachment of myeloma cells to multiple myeloma (MM) bone marrow stroma. The alternatively-spliced CS-1 region of fibronectin (FN) and VCAM-1 are main ligands for VLA-4 and are both expressed on MM stroma. The Iii region is present in all FN isoforms and represents an additional binding site for VLA-4. We employed FN fragments FN-H89 and FN-HO, that contain either the CS-1 and Hi, or only the Hi sites, respectively, as well as soluble VCAM-1 (sVCAM-1), to characterize VLA-4-mediated adhesion pathways used by myeloma cells to attach to MM stroma. CD38(high)CD45RA(-) cells from MM bone marrow, and the myeloma-derived cell lines NCI-H929, IM-9 and RPMI 8226, specifically adhered, by different degrees, to FN-H89, FN-HO and sVCAM-1, and their VLA-4-dependent adhesion was substantially up-regulated by the anti-beta 1 antibody TS2/16, which increases the affinity of VLA-beta 1 integrins. Furthermore, VLA-4 function on NCI-H929 cells was enhanced by TS2/16 during adhesion to MM stroma. The alpha 4 beta 7 integrin mediated a small portion of myeloma cell line adhesion to FN-H89, mainly upon integrin activation with Mn2+. These results indicate that myeloma cells use VLA-4 to interact with CS-1/FN, H1/FN and VCAM-1 on MM stroma, and that its function can be potentially upregulated, enabling higher degrees of cell adhesion to these VLA-4 ligands, which might influence myeloma cell localization in the bone marrow.
引用
收藏
页码:825 / 834
页数:10
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