TY - JOUR
T1 - Eosinophils and megakaryocytes support the early growth of murine MOPC315 myeloma cells in their bone marrow niches
AU - Wong, David
AU - Winter, Oliver
AU - Hartig, Christina
AU - Siebels, Svenja
AU - Szyska, Martin
AU - Tiburzy, Benjamin
AU - Meng, Lingzhang
AU - Kulkarni, Upasana
AU - Fähnrich, Anke
AU - Bommert, Kurt
AU - Bargou, Ralf
AU - Berek, Claudia
AU - Chu, Van Trung
AU - Bogen, Bjarne
AU - Jundt, Franziska
AU - Manz, Rudolf Armin
N1 - Publisher Copyright:
© 2014 Wong et al.
PY - 2014/10/1
Y1 - 2014/10/1
N2 - 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 DdblGATA-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.
AB - 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 DdblGATA-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.
UR - http://www.scopus.com/inward/record.url?scp=84907523497&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0109018
DO - 10.1371/journal.pone.0109018
M3 - Journal articles
C2 - 25272036
AN - SCOPUS:84907523497
VL - 9
JO - PLoS ONE
JF - PLoS ONE
IS - 10
M1 - 109018
ER -