title: Eosinophils and megakaryocytes support the early growth of murine MOPC315 myeloma cells in their bone marrow niches.
abstract: Multiple myeloma is a bone marrow plasma cell tumor which is supported by the external growth factors APRIL and IL-6, among others. Recently, we identified eosinophils and megakaryocytes to be functional components of the micro-environmental niches of benign bone marrow plasma cells and to be important local sources of these cytokines. Here, we investigated whether eosinophils and megakaryocytes also support the growth of tumor plasma cells in the MOPC315.BM model for multiple myeloma. As it was shown for benign plasma cells and multiple myeloma cells, IL-6 and APRIL also supported MOPC315.BM cell growth in vitro, IL-5 had no effect. Depletion of eosinophils in vivo by IL-5 blockade led to a reduction of the early myeloma load. Consistent with this, myeloma growth in early stages was retarded in eosinophil-deficient ΔdblGATA-1 mice. Late myeloma stages were unaffected, possibly due to megakaryocytes compensating for the loss of eosinophils, since megakaryocytes were found to be in contact with myeloma cells in vivo and supported myeloma growth in vitro. We conclude that eosinophils and megakaryocytes in the niches for benign bone marrow plasma cells support the growth of malignant plasma cells. Further investigations are required to test whether perturbation of these niches represents a potential strategy for the treatment of multiple myeloma.
authors.affiliation: University of Lübeck, Institute for Systemic Inflammation Research, ISEF, Lübeck, Germany.
authors.forename: David
authors.initials: D
authors.lastname: Wong
authors.affiliation: Charité - University Medicine Berlin, Department of Rheumatology and German Arthritis Research Center DRFZ, Berlin, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Winter
authors.affiliation: University of Lübeck, Institute for Systemic Inflammation Research, ISEF, Lübeck, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Hartig
authors.affiliation: University of Lübeck, Institute for Systemic Inflammation Research, ISEF, Lübeck, Germany.
authors.forename: Svenja
authors.initials: S
authors.lastname: Siebels
authors.affiliation: University of Lübeck, Institute for Systemic Inflammation Research, ISEF, Lübeck, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Szyska
authors.affiliation: University of Lübeck, Institute for Systemic Inflammation Research, ISEF, Lübeck, Germany.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Tiburzy
authors.affiliation: University of Lübeck, Institute for Systemic Inflammation Research, ISEF, Lübeck, Germany.
authors.forename: Lingzhang
authors.initials: L
authors.lastname: Meng
authors.affiliation: University of Lübeck, Institute for Systemic Inflammation Research, ISEF, Lübeck, Germany.
authors.forename: Upasana
authors.initials: U
authors.lastname: Kulkarni
authors.affiliation: University of Lübeck, Institute for Anatomy, Lübeck, Germany.
authors.forename: Anke
authors.initials: A
authors.lastname: Fähnrich
authors.affiliation: Comprehensive Cancer Centre Mainfranken, University Hospital Würzburg, Würzburg, Germany.
authors.forename: Kurt
authors.initials: K
authors.lastname: Bommert
authors.affiliation: Department of Internal Medicine II, Division of Haematology and Medical Oncology, University Hospital Würzburg, Würzburg, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Bargou
authors.affiliation: German Arthritis Research Center (DRFZ Berlin), Berlin, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Berek
authors.affiliation: German Arthritis Research Center (DRFZ Berlin), Berlin, Germany.
authors.forename: Van Trung
authors.initials: VT
authors.lastname: Chu
authors.affiliation: Centre for Immune Regulation, Institute of Immunology, University of Oslo and Oslo University Hospital, Oslo, Norway.
authors.forename: Bjarne
authors.initials: B
authors.lastname: Bogen
authors.affiliation: Department of Internal Medicine II, Division of Haematology and Medical Oncology, University Hospital Würzburg, Würzburg, Germany.
authors.forename: Franziska
authors.initials: F
authors.lastname: Jundt
authors.affiliation: University of Lübeck, Institute for Systemic Inflammation Research, ISEF, Lübeck, Germany.
authors.forename: Rudolf Armin
authors.initials: RA
authors.lastname: Manz
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000473:pathology*; D049109:Cell Proliferation; D018920:Coculture Techniques; D004804:Eosinophils / Q000166:cytology*; D008533:Megakaryocytes / Q000166:cytology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009101:Multiple Myeloma / Q000473:pathology*