title: Granulocyte-like myeloid derived suppressor cells (G-MDSC) are increased in multiple myeloma and are driven by dysfunctional mesenchymal stem cells (MSC).
abstract: Granulocytic-Myeloid-derived suppressor cells (G-MDSC) are increased in Multiple Myeloma (MM) patients but the mechanisms of G-MDSC generation are still unknown. There are many evidences of the role of mesenchymal stem cells (MSC) in promoting MM cell growth, survival and drug-resistance. We here used a specific experimental model in vitro to evaluate the ability of MSC to induce G-MDSC. We found that although MSC derived from healthy donors (HD), MGUS and MM were able to generate the same amount of MDSC, only MM-MSC-educated G-MDSC exhibited suppressive ability. In addition, in comparison with MSC derived from HD, MM-MSC produce higher amount of immune-modulatory factors that could be involved in MDSC induction. Compared to G-MDSC obtained from co-culture models with MSC from healthy subjects, both MGUS and MM-MSC-educated G-MDSC showed increase of immune-modulatory factors. However, only MM-MSC educated G-MDSC 1) up-regulated immune-suppressive factors as ARG1 and TNFα, 2) expressed higher levels of PROK2, important in angiogenesis and inflammatory process, and 3) showed ability to digest bone matrix.Our data demonstrate that MM-MSC are functionally different from healthy subjects and MGUS-MSC, supporting an evolving concept regarding the contribution of MM-MSC to tumor development and progression.
authors.affiliation: Division of Hematology, A.O.U. Policlinico-OVE, Catania, University of Catania, Italy.|Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy.
authors.forename: Cesarina
authors.initials: C
authors.lastname: Giallongo
authors.affiliation: Division of Hematology, A.O.U. Policlinico-OVE, Catania, University of Catania, Italy.|Department of Biological, Geological and Environmental Sciences, University of Catania, Catania, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Tibullo
authors.affiliation: Division of Hematology, A.O.U. Policlinico-OVE, Catania, University of Catania, Italy.
authors.forename: Nunziatina L
authors.initials: NL
authors.lastname: Parrinello
authors.affiliation: Division of Hematology, A.O.U. Policlinico-OVE, Catania, University of Catania, Italy.
authors.forename: Piera
authors.initials: P
authors.lastname: La Cava
authors.affiliation: Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy.
authors.forename: Michelino
authors.initials: M
authors.lastname: Di Rosa
authors.affiliation: Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Bramanti
authors.affiliation: Division of Hematology, A.O.U. Policlinico-OVE, Catania, University of Catania, Italy.
authors.forename: Cosimo
authors.initials: C
authors.lastname: Di Raimondo
authors.affiliation: Division of Hematology, A.O.U. Policlinico-OVE, Catania, University of Catania, Italy.
authors.forename: Concetta
authors.initials: C
authors.lastname: Conticello
authors.affiliation: Division of Hematology, A.O.U. Policlinico-OVE, Catania, University of Catania, Italy.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Chiarenza
authors.affiliation: Division of Hematology, A.O.U. Policlinico-OVE, Catania, University of Catania, Italy.
authors.forename: Giuseppe A
authors.initials: GA
authors.lastname: Palumbo
authors.affiliation: Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Avola
authors.affiliation: Division of Hematology, A.O.U. Policlinico-OVE, Catania, University of Catania, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Romano
authors.affiliation: Division of Hematology, A.O.U. Policlinico-OVE, Catania, University of Catania, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Di Raimondo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006098:Granulocytes / Q000502:physiology*; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D008875:Middle Aged; D009101:Multiple Myeloma / Q000209:etiology / Q000276:immunology*; D000072737:Myeloid-Derived Suppressor Cells / Q000502:physiology*; D059016:Tumor Microenvironment
keywords: G-MDSC; MM microenvironemnt; immune-suppression; mesenchymal stem cells