Mn2+ regulates myeloma cell adhesion differently than the proadhesive cytokines HGF, IGF-1, and SDF-1α

Authors

  • Tobias S. Slørdahl,

    1. Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
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  • Håkon Hov,

    1. Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
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  • Randi U. Holt,

    1. Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
    2. Faculty of Food and Medical Technology, Sør-Trøndelag University College, Trondheim, Norway
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  • Vadim Baykov,

    1. Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
    2. Department of Pathology, St Petersburg State Medical University, St Petersburg, Russia
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  • Tore Syversen,

    1. Department of Neuroscience, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
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  • Anders Sundan,

    1. Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
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  • Anders Waage,

    1. Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
    2. Department of Hematology, St Olavs University Hospital, Trondheim, Norway
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  • Magne Børset

    1. Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
    2. Department of Immunology and Transfusion Medicine, St Olavs University Hospital, Trondheim, Norway
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Tobias Schmidt Slørdahl, Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Medisinsk teknisk forskningssenter, N-7489 Trondheim, Norway. Tel: +47 73550290; Fax: +47 73598801; e-mail: tobiassc@stud.ntnu.no

Abstract

Adhesion of multiple myeloma (MM) cells in the bone marrow (BM) is important for the growth and survival of the myeloma cells. Very late antigen-4 (VLA-4) is one of the main adhesion receptors that mediate MM cell binding to fibronectin (FN). In this study we have examined the effect of divalent cations on adhesion of MM cells to FN, and compared this type of adhesion with the adhesion induced by the cytokines HGF, IGF-1 and SDF-1α. Mn2+ induced adhesion in all cell lines tested. Cytokine- and Mn2+-induced VLA-4-mediated adhesion were different in many respects, including binding specificity, adhesion kinetics and the activation state of VLA-4. To study a potential role of divalent cations in vivo, we measured the concentrations of divalent cations in BM plasma from 14 MM patients. We also found that Mn2+-mediated adhesion to FN activated the MAPK pathway, indicating that the interaction of MM-cells with FN mediated by Mn2+ could play a critical role for growth and proliferation. In conclusion, this study shows a potential important role of divalent cations in MM cell biology and supports earlier studies pointing to activated VLA-4 as a key for homing of MM cells to the BM.

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