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Granulocyte-like myeloid derived suppressor cells (G-MDSC) are increased in multiple myeloma and are driven by dysfunctional mesenchymal stem cells (MSC)

2016; Impact Journals LLC; Volume: 7; Issue: 52 Linguagem: Inglês

10.18632/oncotarget.7969

1949-2553

Cesarina Giallongo, Daniele Tibullo, Nunziatina Laura Parrinello, Piera La Cava, Michelino Di Rosa, Vincenzo Bramanti, Cosimo Di Raimondo, Concetta Conticello, Annalisa Chiarenza, Giuseppe A. Palumbo, Roberto Avola, Alessandra Romano, Francesco Di Raimondo,

Histone Deacetylase Inhibitors Research

// Cesarina Giallongo 1, 2, * , Daniele Tibullo 1, 3, * , Nunziatina L. Parrinello 1 , Piera La Cava 1 , Michelino Di Rosa 2 , Vincenzo Bramanti 2 , Cosimo Di Raimondo 1 , Concetta Conticello 1 , Annalisa Chiarenza 1 , Giuseppe A. Palumbo 1 , Roberto Avola 2 , Alessandra Romano 1, * , Francesco Di Raimondo 1, * 1 Division of Hematology, A.O.U. Policlinico-OVE, Catania, University of Catania, Italy 2 Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy 3 Department of Biological, Geological and Environmental Sciences, University of Catania, Catania, Italy * These authors contributed equally to this work Correspondence to: Daniele Tibullo, email: d.tibullo@unict.it Keywords: MM microenvironemnt, mesenchymal stem cells, G-MDSC, immune-suppression Received: October 30, 2015 Accepted: February 05, 2016 Published: March 07, 2016 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.