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Significance of VLA-4–VCAM-1 interaction and CD44 for transendothelial invasion in a bone marrow metastatic myeloma model

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Abstract

In previous work, we established the B9/BM1 syngeneic murine bone marrow metastasis model. Interleukin (IL)-6-dependent, IL-1-producing B9/BM1 cells, which colonize the vertebral and femoral marrow after i.v. injection, show great similarity in cell surface phenotype to human myeloma cells, especially the expression of 3 adhesion molecules, CD44, VLA-4 and ICAM-1. Here we investigated the function of these adhesion molecules by binding and transendothelial invasion assays using a newly established bone marrow-derived endothelial cell line (BMEC). A combination of monoclonal antibodies against CD44 and VLA-4 significantly inhibited the adherence of B9/BM1 cells to BMEC and anti-CD44 mAb especially blocked B9/BM1 transendothelial invasion of unstimulated BMEC cells. Results of additional experiments, in which the cells were treated with anti-CD44 and hyaluronidase, demonstrated that the interaction of CD44 molecules on B9/BM1 cells with hyaluronan on BMEC cells was a critical factor in both adhesion and transendothelial invasion in this model. However, stimulation of BMEC with TNFα resulted in increased invasion by B9/BM1 cells, which was completely suppressed by anti-VCAM-1 mAb, implicating a significant role of this adhesion molecule in this process during inflammation.

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Authors and Affiliations

  1. Biomolecules Department, National Institute of Bioscience and Human-Technology, 1-1 Higashi, Tsukuba, 305-8566, Japan

    Tomoko Okada, Masato Kodaka & Hiroaki Okuno

  2. Holland Laboratory, American Red Cross, Hematopoiesis Department, Rockville, Maryland, USA

    Robert G. Hawley

Authors
  1. Tomoko Okada
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  2. Robert G. Hawley
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  3. Masato Kodaka
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  4. Hiroaki Okuno
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Okada, T., Hawley, R.G., Kodaka, M. et al. Significance of VLA-4–VCAM-1 interaction and CD44 for transendothelial invasion in a bone marrow metastatic myeloma model. Clin Exp Metastasis 17, 623–629 (1999). https://doi.org/10.1023/A:1006715504719

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