title: Characterization of VLA-4-dependent myeloma cell adhesion to fibronectin and VCAM-1.
abstract: 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 H1 region is present in all FN isoforms and represents an additional binding site for VLA-4. We employed FN fragments FN-H89 and FN-H0, that contain either the CS-1 and H1, or only the H1 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. CD38highCD45RA- 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-H0 and sVCAM-1, and their VLA-4-dependent adhesion was substantially up-regulated by the anti-beta1 antibody TS2/16, which increases the affinity of VLA-beta1 integrins. Furthermore, VLA-4 function on NCI-H929 cells was enhanced by TS2/16 during adhesion to MM stroma. The alpha4beta7 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 up-regulated, enabling higher degrees of cell adhesion to these VLA-4 ligands, which might influence myeloma cell localization in the bone marrow.
authors.affiliation: Centro de Investigaciones Biológicas, Departamento de Inmunología.
authors.forename: F
authors.initials: F
authors.lastname: Sanz-Rodríguez
authors.forename: N
authors.initials: N
authors.lastname: Ruiz-Velasco
authors.forename: D
authors.initials: D
authors.lastname: Pascual-Salcedo
authors.forename: J
authors.initials: J
authors.lastname: Teixidó
mesh_terms: D018926:Anti-Allergic Agents / Q000378:metabolism*; D002448:Cell Adhesion / Q000502:physiology; D005353:Fibronectins / Q000378:metabolism*; D006801:Humans; D039041:Integrin alpha4beta1; D016023:Integrins / Q000378:metabolism*; D009101:Multiple Myeloma / Q000378:metabolism*; D016201:Receptors, Lymphocyte Homing / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D015854:Up-Regulation; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism*
chemical_list: D018926:Anti-Allergic Agents; D005353:Fibronectins; D039041:Integrin alpha4beta1; D016023:Integrins; D016201:Receptors, Lymphocyte Homing; D019010:Vascular Cell Adhesion Molecule-1