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Expression and function of chemokine receptors in human multiple myeloma

Leukemia volume 17, pages 203–210 (2003)Cite this article

Abstract

Multiple myeloma (MM) is a B cell tumor characterized by its selective localization in the bone marrow. The mechanisms that contribute to the multiple myeloma cell recruitment to the bone marrow microenvironment are not well understood. Chemokines play a central role for lymphocyte trafficking and homing. In this study we have investigated expression and functional importance of chemokine receptors in MM-derived cell lines and primary MM cells. We found that MM cell lines express functional CCR1, CXCR3 and CXCR4 receptors, and some also CCR6. Although only a minority of the cell lines responded by calcium mobilization after agonist stimulation, a migratory response to the CCR1 ligands RANTES and MIP-1α was obtained in 5/6 and 4/6, respectively, of the cell lines tested. Five out of six cell lines showed a response to the CXCR4 ligand SDF-1. In addition, 3/6 cell lines migrated in response to MIP-3α and IP-10, ligands for CCR6 and CXCR3, respectively. The expression of CXCR4 and CCR1 and the migration to their ligands, SDF-1, and RANTES and MIP-1α, respectively, were also demonstrated in primary MM cells. These findings suggest that chemokine receptor expression and the migratory capacity of MM cells to their ligands are relevant for the compartmentalization of MM cells in the bone marrow.

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Acknowledgements

We thank Drs Karl Åkerman and Jyrki Kukkonen for help with [Ca2+]i-analysis and Dr A Österborg, Karolinska Hospital, Stockholm, for providing the MM tumour samples. This work was supported by grants from the Swedish Cancer Society, Hans von Kantzow's Foundation, Ollie and Elof Ericsson's foundation, Erik, Karin and Gösta Selander's Foundation, and Göran Gustafsson's Foundation.

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  1. Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden

    C Möller, T Strömberg, M Juremalm, K Nilsson & G Nilsson

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Möller, C., Strömberg, T., Juremalm, M. et al. Expression and function of chemokine receptors in human multiple myeloma. Leukemia 17, 203–210 (2003). https://doi.org/10.1038/sj.leu.2402717

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