Oncotarget

Research Papers:

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

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

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Oncotarget. 2016; 7:85764-85775. https://doi.org/10.18632/oncotarget.7969

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Abstract

Cesarina Giallongo1,2,*, Daniele Tibullo1,3,*, Nunziatina L. Parrinello1, Piera La Cava1, Michelino Di Rosa2, Vincenzo Bramanti2, Cosimo Di Raimondo1, Concetta Conticello1, Annalisa Chiarenza1, Giuseppe A. Palumbo1, Roberto Avola2, Alessandra Romano1,*, Francesco Di Raimondo1,*

1Division of Hematology, A.O.U. Policlinico-OVE, Catania, University of Catania, Italy

2Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy

3Department of Biological, Geological and Environmental Sciences, University of Catania, Catania, Italy

*These authors contributed equally to this work

Correspondence to:

Daniele Tibullo, email: [email protected]

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.


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