Oncotarget

Research Papers:

Mesangiogenic progenitor cells are forced toward the angiogenic fate, in multiple myeloma

Simone Pacini, Marina Montali, Francesco Mazziotta, Claudia P. Schifone, Lucia Macchia, Vittoria Carnicelli, Francesca M. Panvini, Serena Barachini, Laura Notarfranchi, Giovanni Battista Previti, Gabriele Buda and Mario Petrini

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Oncotarget. 2019; 10:6781-6790. https://doi.org/10.18632/oncotarget.27285

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Abstract

Simone Pacini1, Marina Montali1, Francesco Mazziotta2, Claudia P. Schifone1, Lucia Macchia3, Vittoria Carnicelli4, Francesca M. Panvini5, Serena Barachini1, Laura Notarfranchi6, Giovanni Battista Previti7, Gabriele Buda1 and Mario Petrini1

1 Department of Clinical and Experimental Medicine, Hematology Division, University of Pisa, Pisa, Italy

2 GeNOMEC School of Doctorate, University of Siena, Siena, Italy

3 Department of Laboratory Medicine, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy

4 Department of Surgical, Medical, and Molecular Pathology and Critical Care Medicine, University of Pisa, Pisa, Italy

5 Institute of Life Sciences, Sant’Anna School of Advanced Studies, Pisa, Italy

6 Department of Medicine and Surgery, Hematology Division, University of Parma, Parma, Italy

7 Unit of Anesthesia and Intensive Care, University of Sassari, Sassari, Italy

Correspondence to:

Simone Pacini,email: simone.pacini@do.unipi.it

Keywords: multiple myeloma; bone marrow microenvironment; angiogenesis; osteogenesis; mesangiogenic progenitor cells

Received: July 18, 2019     Accepted: October 04, 2019     Published: November 26, 2019

ABSTRACT

Multiple myeloma (MM) progresses mainly in the bone marrow where the involvement of a specific microenvironment plays a critical role in maintaining plasma cell growth, spread, and survival. In active disease, the switch from a pre-vascular/non-active phase to a vascular phase is coupled with the impairment of bone turnover. Previously, we have isolated Mesangiogenic Progenitor Cells (MPCs), a bone marrow population that showed mesengenic and angiogenic potential, both in vitro and in vivo. MPC differentiation into musculoskeletal tissue and their ability of sprouting angiogenesis are mutually exclusive, suggesting a role in the imbalancing of the microenvironment in multiple myeloma.

MPCs from 32 bone marrow samples of multiple myeloma and 23 non-hematological patients were compared in terms of frequency, phenotype, mesengenic/angiogenic potential, and gene expression profile. Defective osteogenesis was recorded for MM-derived MPCs that showed longer angiogenic sprouting distances respect to non-hematological MPCs, retaining this capability after mesengenic induction. This altered MPCs differentiation potential was not detected in asymptomatic myelomatous disease.

These in vitro experiments are suggestive of a forced angiogenic fate in MPCs isolated from MM patients, which also showed increased sprouting activity. Taking together our results suggest a possible role of these cells in the “angiogenic switch” in the MM micro-environment.


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