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PMID: 10845562 Published · ppublish English Journal Article

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

Clinical & experimental metastasis ·Vol. 17 ·No. 7 ·1999-00-00 ·Pages 623-9

Okada T, Hawley RG, Kodaka M, Okuno H

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 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.

MeSH Terms
Animals Antibodies, Monoclonal/immunology,pharmacology Bone Marrow/pathology Bone Marrow Cells/cytology,drug effects Cell Adhesion Cell Line/drug effects Coculture Techniques Endothelium/cytology,drug effects Female Hyaluronan Receptors/immunology,physiology Hyaluronic Acid/metabolism,pharmacology Hyaluronoglucosaminidase/pharmacology Integrin alpha4beta1 Integrins/immunology,physiology Mice Mice, Inbred BALB C Multiple Myeloma/pathology Neoplasm Invasiveness/physiopathology Neoplasm Proteins/antagonists & inhibitors,immunology,physiology Receptors, Lymphocyte Homing/immunology,physiology Tumor Cells, Cultured Tumor Necrosis Factor-alpha/pharmacology Vascular Cell Adhesion Molecule-1/immunology,physiology
Chemicals
Antibodies, Monoclonal Hyaluronan Receptors Integrin alpha4beta1 Integrins Neoplasm Proteins Receptors, Lymphocyte Homing Tumor Necrosis Factor-alpha Vascular Cell Adhesion Molecule-1 Hyaluronic Acid Hyaluronoglucosaminidase
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Okada T
Biomolecules Department, National Institute of Bioscience and Human-Technology, Tsukuba, Japan. okada@nibh.go.jp
Hawley R G
Kodaka M
Okuno H
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Article Info
Journal
Clinical & experimental metastasis
Abbr.
Clin Exp Metastasis
ISSN
0262-0898
DOI
10.1023/a:1006715504719
Email
okada@nibh.go.jp
Published
1999-00-00
Pages
623-9
Language
English
Region
Netherlands
NLM ID
8409970
Subset
IM
External Links
PubMed source DOI: 10.1023/a:1006715504719 View journal details
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