Monocyte chemoattractant protein-1 (MCP-1), secreted by bone marrow endothelial cells, induces chemoattraction of 5T multiple myeloma cells.
Homing of multiple myeloma (MM) cells to the bone marrow (BM) requires transendothelial migration. In the present work we tested whether monocyte chemoattractant protein-1 (MCP-1) and CCR2, the high affinity receptor for MCP-1, are involved in this process. Murine 5T2 and 5T33MM cell lines were selected as source of MM cells and STR4, 10 and 12 of BM endothelial cells (BMEC). RT-PCR demonstrated transcripts for MCP-1 in BMEC and ELISA the presence of MCP-1 protein in culture medium. RNase protection assay showed mRNA expression for CCR2, and FACS analysis the presence of CCR2 protein on the MM cells. EC conditioned medium induced chemoattraction of MM cells, a phenomenon inhibited by anti-MCP-1 antibodies. In conclusion, MM cells express CCR2 and are attracted by MCP-1 secreted by BMEC. We suggest that local MCP-1 production by BMEC is one of the mechanisms involved in homing of myeloma cells to the BM.
Vanderkerken
Karin
K
Department of Hematology and Immunology, Free University Brussels (VUB), Belgium. Karin.Vanderkerken@vub.ac.be
Vande Broek
Isabelle
I
Eizirik
Décio L
DL
Van Valckenborgh
Els
E
Asosingh
Kewal
K
Van Riet
Ivan
I
Van Camp
Ben
B
D000818:Animals; D001853:Bone Marrow / Q000378:metabolism*; D002461:Cell Line, Transformed; D018932:Chemokine CCL2 / Q000378:metabolism / Q000494:pharmacology*; D002633:Chemotaxis / Q000187:drug effects*; D004727:Endothelium / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009101:Multiple Myeloma / Q000235:genetics / Q000473:pathology*; D009363:Neoplasm Proteins / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis; D012334:RNA, Neoplasm / Q000032:analysis; D054390:Receptors, CCR2; D019707:Receptors, Chemokine / Q000187:drug effects / Q000235:genetics / Q000502:physiology
C515335:Ccr2 protein, mouse; D018932:Chemokine CCL2; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D054390:Receptors, CCR2; D019707:Receptors, Chemokine