Abstract
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.
MeSH Terms
Animals
Bone Marrow/metabolism
Cell Line, Transformed
Chemokine CCL2/metabolism,pharmacology
Chemotaxis/drug effects
Endothelium/metabolism,pathology
Mice
Mice, Inbred C57BL
Multiple Myeloma/genetics,pathology
Neoplasm Proteins/drug effects,genetics,physiology
RNA, Messenger/analysis
RNA, Neoplasm/analysis
Receptors, CCR2
Receptors, Chemokine/drug effects,genetics,physiology
Chemicals
Ccr2 protein, mouse
Chemokine CCL2
Neoplasm Proteins
RNA, Messenger
RNA, Neoplasm
Receptors, CCR2
Receptors, Chemokine
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Vanderkerken Karin
Department of Hematology and Immunology, Free University Brussels (VUB), Belgium. Karin.Vanderkerken@vub.ac.be
Vande Broek Isabelle
Eizirik Décio L
Van Valckenborgh Els
Asosingh Kewal
Van Riet Ivan
Van Camp Ben
References (13)
13 references, click to expand
-
Transendothelial migration of CD34+ and mature hematopoietic cells: an in vitro study using a human bone marrow endothelial cell line.
Blood. 1997 Jan 1;89(1):72-80
PMID: 8978279
-
Identification of IL-1beta-induced messenger RNAs in rat pancreatic beta cells by differential display of messenger RNA.
Diabetologia. 1999 Oct;42(10):1199-203
PMID: 10525660
-
Characterization of the CCR2 chemokine receptor: functional CCR2 receptor expression in B cells.
J Immunol. 1997 Dec 1;159(11):5576-84
PMID: 9548499
-
The 5TMM series: a useful in vivo mouse model of human multiple myeloma.
Hematol J. 2000;1(5):351-6
PMID: 11920212
-
Human monocyte chemoattractant protein-1 (MCP-1).
Immunol Today. 1990 Mar;11(3):97-101
PMID: 2186747
-
Lymphocyte homing and homeostasis.
Science. 1996 Apr 5;272(5258):60-6
PMID: 8600538
-
Monocyte chemotactic and activating factor gene expression induced in endothelial cells by IL-1 and tumor necrosis factor.
J Immunol. 1990 Apr 15;144(8):3034-8
PMID: 2182712
-
Insulin-like growth factor-1 acts as a chemoattractant factor for 5T2 multiple myeloma cells.
Blood. 1999 Jan 1;93(1):235-41
PMID: 9864166
-
Organ involvement and phenotypic adhesion profile of 5T2 and 5T33 myeloma cells in the C57BL/KaLwRij mouse.
Br J Cancer. 1997;76(4):451-60
PMID: 9275021
-
Selective initial in vivo homing pattern of 5T2 multiple myeloma cells in the C57BL/KalwRij mouse.
Br J Cancer. 2000 Feb;82(4):953-9
PMID: 10732771
-
Idiopathic paraproteinemia. II. Transplantation of the paraprotein-producing clone from old to young C57BL/KaLwRij mice.
J Immunol. 1979 Feb;122(2):609-13
PMID: 368243
-
Selective transendothelial migration of hematopoietic progenitor cells: a role in homing of progenitor cells.
Blood. 1999 Jan 1;93(1):149-56
PMID: 9864156
-
Evidence that multiple myeloma Ig heavy chain VDJ genes contain somatic mutations but show no intraclonal variation.
Blood. 1992 Nov 1;80(9):2326-35
PMID: 1421403