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Vicious cycle between myeloma cell binding to bone marrow stromal cells via VLA-4–VCAM-1 adhesion and macrophage inflammatory protein-1α and MIP-1β production

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Abstract

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)-1α and MIP-1β 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-1α and MIP-1β production from MM cells and enhanced production of osteoclastogenic activity by MM cells. Blockade of MIP-1α and MIP-1β 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.

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Acknowledgments

We thank Ms. Hiroe Amou, Ms. Asuka Oda, and Dr. Masahiro Hiasa for their expert technical assistance. This work was supported in part by Grants-in-Aid for Scientific Research (A) to T. M. and (C) to M. A., and for the 21st Century Center of Excellence Program from the Ministry of Education, Culture, Science, and Sports of Japan, and a Grant-in-Aid for Cancer Research (17-16) from the Ministry of Health, Labor, and Welfare of Japan.

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Authors and Affiliations

  1. Department of Medicine and Bioregulatory Sciences, University of Tokushima Graduate School of Medical Sciences, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan

    Masahiro Abe & Toshio Matsumoto

  2. Yokota Orthodontic Institute, Tokushima University Hospital, Tokushima, Japan

    Kenji Hiura

  3. Division of Transfusion Medicine, Tokushima University Hospital, Tokushima, Japan

    Shuji Ozaki

  4. 21st Century Center of Excellence Program of the University of Tokushima, Tokushima, Japan

    Shinsuke Kido

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  1. Masahiro Abe
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  2. Kenji Hiura
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  3. Shuji Ozaki
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  4. Shinsuke Kido
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  5. Toshio Matsumoto
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Correspondence to Masahiro Abe.

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Abe, M., Hiura, K., Ozaki, S. et al. Vicious cycle between myeloma cell binding to bone marrow stromal cells via VLA-4–VCAM-1 adhesion and macrophage inflammatory protein-1α and MIP-1β production. J Bone Miner Metab 27, 16–23 (2009). https://doi.org/10.1007/s00774-008-0012-z

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  • DOI: https://doi.org/10.1007/s00774-008-0012-z

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