Eosinophils and Megakaryocytes Support the Early Growth of Murine MOPC315 Myeloma Cells in Their Bone Marrow Niches

Please always quote using this URN: urn:nbn:de:bvb:20-opus-115269
  • 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 multipleMultiple 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 Delta dblGATA-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.show moreshow less

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Metadaten
Author: David Wong, Oliver Winter, Christina Hartig, Svenja Siebels, Martin Szyska, Benjamin Tiburzy, Lingzhang Meng, Upasana Kulkarni, Anke Fähnrich, Kurt Bommert, Ralf Bargou, Claudia Berek, Trung Chu Van, Bjarne Bogen, Franziska Jundt, Rudolf Armin Manz
URN:urn:nbn:de:bvb:20-opus-115269
Document Type:Journal article
Faculties:Medizinische Fakultät / Medizinische Klinik und Poliklinik II
Language:English
Parent Title (English):PLOS ONE
Year of Completion:2014
Volume:9
Issue:10
Pagenumber:e109018
Source:PLoS ONE 9(10): e109018. doi:10.1371/journal.pone.0109018
DOI:https://doi.org/10.1371/journal.pone.0109018
Pubmed Id:http://www.ncbi.nlm.nih.gov/pubmed?term=25272036
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Tag:B-cells; Interleukin-5; april; dexamethasone; human multiple-myeloma; immune response; plasma cells; receptor expression; stromal cells; survival
Release Date:2015/07/14
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung