Chemokine receptor CCR2 is expressed by human multiple myeloma cells and mediates migration to bone marrow stromal cell-produced monocyte chemotactic proteins MCP-1, -2 and -3

• Published in: British journal of cancer Vol. 88; no. 6; pp. 855 - 862
• Main Authors: VANDE BROEK, I, ASOSINGH, K, VANDERKERKEN, K, STRAETMANS, N, VAN CAMP, B, VAN RIET, I
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 24.03.2003
• Subjects: Biological and medical sciences; Bone marrow; Bone Marrow - pathology; Cancer research; Cell Adhesion; Cell Movement; Chemokine CCL2 - biosynthesis; Chemokine CCL7; Chemokine CCL8; Chemokines; Cytokines; Dendritic cells; Gene Expression Regulation, Neoplastic; Hematology; Humans; Immunodeficiencies. Immunoglobulinopathies; Immunoglobulinopathies; Immunopathology; Ligands; Medical research; Medical sciences; Molecular and Cellular Pathology; Monocyte Chemoattractant Proteins - biosynthesis; Multiple myeloma; Multiple Myeloma - genetics; Multiple Myeloma - pathology; Proteins; Receptors, CCR2; Receptors, Chemokine - analysis; Receptors, Chemokine - biosynthesis; Stromal Cells - physiology; Tumor Cells, Cultured; Human; Immunopathology; multiple myeloma; CCR2 chemokine receptor; Malignant hemopathy; Myeloma; chemokines; Cell motility; Immunoglobulinopathy; Lymphoproliferative syndrome; Bone marrow; Homing phenomenon; Stromal cell; homing; Monocyte chemoattractant protein 1; CCR2
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/sj.bjc.6600833

The restricted bone marrow (BM) localisation of multiple myeloma (MM) cells most likely results from a specific homing influenced by chemotactic factors, combined with the proper signals for growth and survival provided by the BM microenvironment. In analogy to the migration and homing of normal lymphocytes, one can hypothesise that the BM homing of MM cells is mediated by a multistep process, involving the concerted action of adhesion molecules and chemokines. In this study, we report that primary MM cells and myeloma derived cell lines (Karpas, LP-1 and MM5.1) express the chemokine receptor CCR2. In addition, we found that the monocyte chemotactic proteins (MCPs) MCP-1, -2 and -3, three chemokines acting as prominent ligands for CCR2, are produced by stromal cells, cultured from normal and MM BM samples. Conditioned medium (CM) from BM stromal cells, as well as MCP-1, -2 and -3, act as chemoattractants for human MM cells. Moreover, a blocking antibody against CCR2, as well as a combination of neutralizing antibodies against MCP-1, -2 and -3, significantly reduced the migration of human MM cells to BM stromal cell CM. The results obtained in this study indicate the involvement of CCR2 and the MCPs in the BM homing of human MM cells.