Significance of VLA-4-VCAM-1 interaction and CD44 for transendothelial invasion in a bone marrow metastatic myeloma model.
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 TNFalpha 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.
Okada
T
T
Biomolecules Department, National Institute of Bioscience and Human-Technology, Tsukuba, Japan. okada@nibh.go.jp
Hawley
R G
RG
Kodaka
M
M
Okuno
H
H
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D001853:Bone Marrow / Q000473:pathology*; D001854:Bone Marrow Cells / Q000166:cytology* / Q000187:drug effects; D002448:Cell Adhesion; D002460:Cell Line / Q000187:drug effects; D018920:Coculture Techniques; D004727:Endothelium / Q000166:cytology / Q000187:drug effects; D005260:Female; D018960:Hyaluronan Receptors / Q000276:immunology / Q000502:physiology*; D006820:Hyaluronic Acid / Q000378:metabolism / Q000494:pharmacology; D006821:Hyaluronoglucosaminidase / Q000494:pharmacology; D039041:Integrin alpha4beta1; D016023:Integrins / Q000276:immunology / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009101:Multiple Myeloma / Q000473:pathology*; D009361:Neoplasm Invasiveness / Q000503:physiopathology*; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000276:immunology / Q000502:physiology*; D016201:Receptors, Lymphocyte Homing / Q000276:immunology / Q000502:physiology*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D019010:Vascular Cell Adhesion Molecule-1 / Q000276:immunology / Q000502:physiology*
D000911:Antibodies, Monoclonal; D018960:Hyaluronan Receptors; D039041:Integrin alpha4beta1; D016023:Integrins; D009363:Neoplasm Proteins; D016201:Receptors, Lymphocyte Homing; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D006820:Hyaluronic Acid; D006821:Hyaluronoglucosaminidase