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Myeloma

CD44 variant isoforms are involved in plasma cell adhesion to bone marrow stromal cells

Leukemia volume 16, pages 135–143 (2002)Cite this article

Abstract

Expression of CD44v9-containing isoforms (CD44v9) on myeloma plasma cells correlates with unfavorable prognosis, suggesting that CD44 variant molecules are involved in the disease process. In this study, the presence of CD44v on B cell lines from different stages of development was analyzed by flow cytometry and a role in adhesion to stromal cells from different tissues was evaluated in in vitro binding assays. CD44v3, v6 and v9 isoforms were exclusively expressed on plasma cell lines and CD44v9 expression correlated with IL-6-dependent plasma cell growth. Binding studies using CD44 isoform- specific reagents showed that CD44v6 and CD44v9 were involved in binding to bone marrow stromal cells, but not to in vitro synthesized ECM or hyaluronic acid. CD44v9-mediated plasma cell binding resulted in a significant induction of IL-6 secretion by bone marrow stromal cells. Large differences in quantitative plasma cell binding to stromal cells from different tissues were observed. These, however, could not be related to a differential use of CD44v in these binding processes. The role of CD44v9 in adhesion induced IL-6 secretion and its preferential expression on IL-6-dependent plasma cell lines may explain the previously observed correlation between CD44v9 expression and adverse prognosis in multiple myeloma.

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Acknowledgements

We thank T Strooisma, Department of Immunology, University Hospital Utrecht, Utrecht, the Netherlands, for performing the IL-6 ELISA, and Dr S Mahlmann, Basel Institute for Immunology, Basel, Switzerland, for critical reading and helpful comments concerning the manuscript. The Basel Institute for Immunology was founded and is supported by F Hoffmann–La Roche Inc., Basel, Switzerland.

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  1. M Van Driel

    Present address: Department of Internal Medicine III, Erasmus Medical Center, Dr Molewaterplein 40, Rotterdam, 3014 GD, The Netherlands

Authors and Affiliations

  1. Department of Immunology, University Hospital Utrecht, Utrecht, The Netherlands

    M Van Driel & AC Bloem

  2. Basel Institute for Immunology, Basel, Switzerland

    U Günthert

  3. Department of Hematology, University Hospital Utrecht, Utrecht, The Netherlands

    AC van Kessel & HM Lokhorst

  4. Department of Pathology, University Hospital Utrecht, Utrecht, The Netherlands

    P Joling

  5. Department of Internal Medicine, University Hospital Innsbruck, Innsbruck, Austria

    R Stauder

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Van Driel, M., Günthert, U., van Kessel, A. et al. CD44 variant isoforms are involved in plasma cell adhesion to bone marrow stromal cells. Leukemia 16, 135–143 (2002). https://doi.org/10.1038/sj.leu.2402336

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