Granulocytic myeloid-derived suppressor cells promote angiogenesis in the context of multiple myeloma
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Marilène Binsfeld1, Joséphine Muller1, Virginie Lamour2, Kim De Veirman3, Hendrik De Raeve4, Akeila Bellahcène2, Els Van Valckenborgh3, Frédéric Baron1, Yves Beguin1, Jo Caers1,*, Roy Heusschen1,*
1Laboratory of Hematology, GIGA-Research, University of Liège, B-4000 Liège, Belgium
2Metastasis Research Laboratory, GIGA-Research, University of Liège, B-4000 Liège, Belgium
3Department of Hematology and Immunology, Myeloma Center Brussels, Vrije Universiteit Brussel, B-1090 Brussels, Belgium
4Department of Pathology, OLV Ziekenhuis Aalst, B-9300 Aalst, Belgium
*These authors have contributed equally to this work
Marilène Binsfeld, email: [email protected]
Keywords: multiple myeloma, myeloid-derived suppressor cells, angiogenesis, pro-angiogenic, osteoclasts
Received: December 11, 2015 Accepted: April 27, 2016 Published: May 10, 2016
Multiple myeloma (MM) is a plasma cell malignancy characterized by the accumulation of tumor cells in the bone marrow (BM) and is associated with immunosuppression, angiogenesis and osteolysis. Myeloid-derived suppressor cells (MDSCs) represent a heterogeneous population of immature, immunosuppressive myeloid cells that promote tumor progression through different mechanisms.
In this work, we studied the contribution of MDSC subsets to different disease-promoting aspects in MM. We observed an expansion of polymorphonuclear/granulocytic (PMN-)MDSCs in two immunocompetent murine MM models, while this was not observed for monocytic (MO-)MDSCs. Both MDSC subpopulations from MM-bearing mice were immunosuppressive, but PMN-MDSCs displayed a higher suppressive potential. Soluble factors secreted by MM cells increased the viability of MDSCs, whereas the presence of MDSCs did not affect the proliferation of MM cells in vitro or in vivo. Interestingly, we observed a pro-angiogenic effect of PMN-MDSCs in the context of MM using the chick chorioallantoic membrane assay. Consistently, MM-derived PMN-MDSCs showed an up-regulation of angiogenesis-related factors and reduced PMN-MDSC levels were associated with less angiogenesis in vivo. Finally, we identified MO-MDSCs as osteoclast precursors.
These results suggest that MDSC subpopulations play diverging roles in MM. We show for the first time that PMN-MDSCs exert a pro-angiogenic role in MM.
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