Vicious cycle between myeloma cell binding to bone marrow stromal cells via VLA-4-VCAM-1 adhesion and macrophage inflammatory protein-1alpha and MIP-1beta production.
Multiple myeloma (MM) cell adhesion to stromal cells via very late antigen (VLA)-4 and vascular cell adhesion molecule (VCAM)-1 interaction causes enhanced secretion of osteoclastogenic activity by MM cells. We have reported that MM cell-derived macrophage inflammatory protein (MIP)-1alpha and MIP-1beta are responsible for most of the osteoclastogenic activity in MM. Thus, adhesion-mediated osteoclastogenesis may be caused by enhanced production of MIP-1 via VLA-4-VCAM-1 interaction. The present study was undertaken to clarify whether MM cell-derived MIP-1 plays a role in VLA-4-VCAM-1 adhesion-mediated osteoclastogenesis. Adhesion of MM cells to VCAM-1 upregulated MIP-1alpha and MIP-1beta production from MM cells and enhanced production of osteoclastogenic activity by MM cells. Blockade of MIP-1alpha and MIP-1beta actions not only abrogated elaboration of osteoclastogenic activity, but also suppressed spontaneous MM cell adhesion to VCAM-1. These results demonstrate that MM cell adhesion to VCAM-1 upregulates MIP-1 production by MM cells to cause enhancement of osteoclastogenesis. In addition, the results suggest that the increased production of MIP-1 further enhances MM cell binding to stromal cells via stimulation of VLA-4-VCAM-1 adhesion, forming a "vicious cycle" between MM cell adhesion to stromal cells and MIP-1 production via VLA-4-VCAM-1 interaction.
Abe
Masahiro
M
Department of Medicine and Bioregulatory Sciences, University of Tokushima Graduate School of Medical Sciences, 3-18-15 Kuramoto-cho, Tokushima 770-8503, Japan. masabe@clin.med.tokushima-u.ac.jp
Hiura
Kenji
K
Ozaki
Shuji
S
Kido
Shinsuke
S
Matsumoto
Toshio
T
D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism*; D002448:Cell Adhesion / Q000502:physiology; D002460:Cell Line; D054405:Chemokine CCL3 / Q000378:metabolism*; D054407:Chemokine CCL4 / Q000378:metabolism*; D006801:Humans; D039041:Integrin alpha4beta1 / Q000378:metabolism*; D051379:Mice; D009101:Multiple Myeloma / Q000473:pathology* / Q000503:physiopathology; D010010:Osteoclasts / Q000166:cytology / Q000502:physiology; D017154:Stromal Cells / Q000378:metabolism*; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism*
D054405:Chemokine CCL3; D054407:Chemokine CCL4; D039041:Integrin alpha4beta1; D019010:Vascular Cell Adhesion Molecule-1