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Characterization of VLA‐4‐dependent myeloma cell adhesion to fibronectin and VCAM‐1
Author(s) -
SanzRodríguez Francisco,
RuizVelasco Natividad,
PascualSalcedo Dora,
Teixidó Joaquin
Publication year - 1999
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.1999.01762.x
Subject(s) - fibronectin , integrin , stroma , cell adhesion , bone marrow , multiple myeloma , chemistry , adhesion , cell adhesion molecule , cell culture , microbiology and biotechnology , cancer research , biology , cell , immunology , biochemistry , immunohistochemistry , genetics , organic chemistry
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. 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‐H0 and sVCAM‐1, and their VLA‐4‐dependent adhesion was substantially up‐regulated by the anti‐β1 antibody TS2/16, which increases the affinity of VLA‐β1 integrins. Furthermore, VLA‐4 function on NCI‐H929 cells was enhanced by TS2/16 during adhesion to MM stroma. The α4β7 integrin mediated a small portion of myeloma cell line adhesion to FN‐H89, mainly upon integrin activation with Mn 2+ . 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.