Mechanisms involved in the differential bone marrow homing of CD45 subsets in 5T murine models of myeloma

  • Kewal Asosingh
  • Eline Menu
  • Els Van Valckenborgh
  • Isabelle Vande Broek
  • Ivan Van Riet
  • Ben Van Camp
  • Karin Vanderkerken
Article

Abstract

Multiple myeloma (MM) is an incurable plasma cell cancer, localized in the bone marrow (BM). The mechanisms used by these cells to (re-)enter this organ remain largely unknown. Recently, we reported that both CD45+ and CD45 myeloma cells home to the BM and induce myeloma disease. In this work, we investigated the underlying mechanisms involved in the homing of CD45+ and CD45 myeloma cells in the experimental 5T2MM and 5T33MM murine models. In vivo tracing of flow cytometric sorted and radioactively labeled CD45 subsets revealed a reduced homing of the CD45 5TMM cells to the BM as compared to the CD45+ 5TMM cells. Migration assays demonstrated an impaired chemotaxis towards BM endothelial cell conditioned medium, BM stromal cell conditioned medium and towards the basement membrane component laminin-1 of the CD45 5TMM cells compared to the CD45+ subset. Matrix metalloproteinase-9 (MMP-9) and urokinase type plasminogen activator (uPA) are key extracellular matrix proteases involved in the invasion of cancer cells. Inhibitor and antibody blocking experiments demonstrated the involvement of both in the invasion of the 5TMM cells. CD45 5TMM cells had a low secretion of MMP-9 and (for the non-aggressive line 5T2MM only) a low cell surface expression of uPA receptor, as revealed by gelatin zymography and flow cytometric analysis, respectively. Accordingly, the synthetic basement membrane invasive capacity of the CD45 5TMM subpopulations was also impaired. Our results indicate that CD45+ and CD45 5T myeloma cells have a differential BM homing attributable to differential migratory and invasive capacities.

adhesion bone marrow CD45 homing invasion migration myeloma 

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Copyright information

© Kluwer Academic Publishers 2002

Authors and Affiliations

  • Kewal Asosingh
    • 1
  • Eline Menu
    • 1
  • Els Van Valckenborgh
    • 1
  • Isabelle Vande Broek
    • 1
  • Ivan Van Riet
    • 1
  • Ben Van Camp
    • 1
  • Karin Vanderkerken
    • 1
  1. 1.Department of Hematology and ImmunologyVrije Universiteit Brussel (VUB)BrusselsBelgium

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