title: Granulocytic myeloid-derived suppressor cells promote angiogenesis in the context of multiple myeloma.
abstract: 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.
authors.affiliation: Laboratory of Hematology, GIGA-Research, University of Liège, B-4000 Liège, Belgium.
authors.forename: Marilène
authors.initials: M
authors.lastname: Binsfeld
authors.affiliation: Laboratory of Hematology, GIGA-Research, University of Liège, B-4000 Liège, Belgium.
authors.forename: Joséphine
authors.initials: J
authors.lastname: Muller
authors.affiliation: Metastasis Research Laboratory, GIGA-Research, University of Liège, B-4000 Liège, Belgium.
authors.forename: Virginie
authors.initials: V
authors.lastname: Lamour
authors.affiliation: Department of Hematology and Immunology, Myeloma Center Brussels, Vrije Universiteit Brussel, B-1090 Brussels, Belgium.
authors.forename: Kim
authors.initials: K
authors.lastname: De Veirman
authors.affiliation: Department of Pathology, OLV Ziekenhuis Aalst, B-9300 Aalst, Belgium.
authors.forename: Hendrik
authors.initials: H
authors.lastname: De Raeve
authors.affiliation: Metastasis Research Laboratory, GIGA-Research, University of Liège, B-4000 Liège, Belgium.
authors.forename: Akeila
authors.initials: A
authors.lastname: Bellahcène
authors.affiliation: Department of Hematology and Immunology, Myeloma Center Brussels, Vrije Universiteit Brussel, B-1090 Brussels, Belgium.
authors.forename: Els
authors.initials: E
authors.lastname: Van Valckenborgh
authors.affiliation: Laboratory of Hematology, GIGA-Research, University of Liège, B-4000 Liège, Belgium.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Baron
authors.affiliation: Laboratory of Hematology, GIGA-Research, University of Liège, B-4000 Liège, Belgium.
authors.forename: Yves
authors.initials: Y
authors.lastname: Beguin
authors.affiliation: Laboratory of Hematology, GIGA-Research, University of Liège, B-4000 Liège, Belgium.
authors.forename: Jo
authors.initials: J
authors.lastname: Caers
authors.affiliation: Laboratory of Hematology, GIGA-Research, University of Liège, B-4000 Liège, Belgium.
authors.forename: Roy
authors.initials: R
authors.lastname: Heusschen
mesh_terms: D000818:Animals; D006098:Granulocytes / Q000378:metabolism*; D006801:Humans; D051379:Mice; D009101:Multiple Myeloma / Q000235:genetics* / Q000473:pathology; D000072737:Myeloid-Derived Suppressor Cells / Q000378:metabolism*; D009389:Neovascularization, Pathologic / Q000378:metabolism* / Q000473:pathology
keywords: angiogenesis; multiple myeloma; myeloid-derived suppressor cells; osteoclasts; pro-angiogenic