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

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 import...

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Autores principales: Wong, David, Winter, Oliver, Hartig, Christina, Siebels, Svenja, Szyska, Martin, Tiburzy, Benjamin, Meng, Lingzhang, Kulkarni, Upasana, Fähnrich, Anke, Bommert, Kurt, Bargou, Ralf, Berek, Claudia, Chu, Van Trung, Bogen, Bjarne, Jundt, Franziska, Manz, Rudolf Armin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4182881/
https://www.ncbi.nlm.nih.gov/pubmed/25272036
http://dx.doi.org/10.1371/journal.pone.0109018
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author Wong, David
Winter, Oliver
Hartig, Christina
Siebels, Svenja
Szyska, Martin
Tiburzy, Benjamin
Meng, Lingzhang
Kulkarni, Upasana
Fähnrich, Anke
Bommert, Kurt
Bargou, Ralf
Berek, Claudia
Chu, Van Trung
Bogen, Bjarne
Jundt, Franziska
Manz, Rudolf Armin
author_facet Wong, David
Winter, Oliver
Hartig, Christina
Siebels, Svenja
Szyska, Martin
Tiburzy, Benjamin
Meng, Lingzhang
Kulkarni, Upasana
Fähnrich, Anke
Bommert, Kurt
Bargou, Ralf
Berek, Claudia
Chu, Van Trung
Bogen, Bjarne
Jundt, Franziska
Manz, Rudolf Armin
author_sort Wong, David
collection PubMed
description 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.
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spelling pubmed-41828812014-10-07 Eosinophils and Megakaryocytes Support the Early Growth of Murine MOPC315 Myeloma Cells in Their Bone Marrow Niches Wong, David Winter, Oliver Hartig, Christina Siebels, Svenja Szyska, Martin Tiburzy, Benjamin Meng, Lingzhang Kulkarni, Upasana Fähnrich, Anke Bommert, Kurt Bargou, Ralf Berek, Claudia Chu, Van Trung Bogen, Bjarne Jundt, Franziska Manz, Rudolf Armin PLoS One Research Article 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. Public Library of Science 2014-10-01 /pmc/articles/PMC4182881/ /pubmed/25272036 http://dx.doi.org/10.1371/journal.pone.0109018 Text en © 2014 Wong et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Wong, David
Winter, Oliver
Hartig, Christina
Siebels, Svenja
Szyska, Martin
Tiburzy, Benjamin
Meng, Lingzhang
Kulkarni, Upasana
Fähnrich, Anke
Bommert, Kurt
Bargou, Ralf
Berek, Claudia
Chu, Van Trung
Bogen, Bjarne
Jundt, Franziska
Manz, Rudolf Armin
Eosinophils and Megakaryocytes Support the Early Growth of Murine MOPC315 Myeloma Cells in Their Bone Marrow Niches
title Eosinophils and Megakaryocytes Support the Early Growth of Murine MOPC315 Myeloma Cells in Their Bone Marrow Niches
title_full Eosinophils and Megakaryocytes Support the Early Growth of Murine MOPC315 Myeloma Cells in Their Bone Marrow Niches
title_fullStr Eosinophils and Megakaryocytes Support the Early Growth of Murine MOPC315 Myeloma Cells in Their Bone Marrow Niches
title_full_unstemmed Eosinophils and Megakaryocytes Support the Early Growth of Murine MOPC315 Myeloma Cells in Their Bone Marrow Niches
title_short Eosinophils and Megakaryocytes Support the Early Growth of Murine MOPC315 Myeloma Cells in Their Bone Marrow Niches
title_sort eosinophils and megakaryocytes support the early growth of murine mopc315 myeloma cells in their bone marrow niches
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4182881/
https://www.ncbi.nlm.nih.gov/pubmed/25272036
http://dx.doi.org/10.1371/journal.pone.0109018
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