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

Br J Haematol. 1999 Dec;107(4):825-34. doi: 10.1046/j.1365-2141.1999.01762.x.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Allergic Agents / metabolism*
  • Cell Adhesion / physiology
  • Fibronectins / metabolism*
  • Humans
  • Integrin alpha4beta1
  • Integrins / metabolism*
  • Multiple Myeloma / metabolism*
  • Receptors, Lymphocyte Homing / metabolism*
  • Tumor Cells, Cultured
  • Up-Regulation
  • Vascular Cell Adhesion Molecule-1 / metabolism*

Substances

  • Anti-Allergic Agents
  • Fibronectins
  • Integrin alpha4beta1
  • Integrins
  • Receptors, Lymphocyte Homing
  • Vascular Cell Adhesion Molecule-1