Research Papers:

Role of erythropoietin in the angiogenic activity of bone marrow endothelial cells of MGUS and multiple myeloma patients

Aurelia Lamanuzzi, Ilaria Saltarella, Arianna Ferrucci, Roberto Ria, Simona Ruggieri, Vito Racanelli, Luigia Rao, Tiziana Annese, Beatrice Nico, Angelo Vacca and Domenico Ribatti _

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Oncotarget. 2016; 7:14510-14521. https://doi.org/10.18632/oncotarget.7587

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Aurelia Lamanuzzi1,*, Ilaria Saltarella1,*, Arianna Ferrucci1, Roberto Ria1, Simona Ruggieri2, Vito Racanelli1, Luigia Rao1, Tiziana Annese2, Beatrice Nico2, Angelo Vacca1, Domenico Ribatti2,3

1Department of Internal Medicine and Clinical Oncology, University of Bari Medical School, Bari, Italy

2Department of Basic Medical Sciences, Neurosciences and Sensory Organs, University of Bari Medical School, Bari, Italy

3National Cancer Institute “Giovanni Paolo II”, Bari, Italy

*These authors contributed equally to this work

Correspondence to:

Domenico Ribatti, e-mail: [email protected]

Keywords: angiogenesis, erythropoietin, endothelial cells, monoclonal gammopathy of undetermined significance, multiple myeloma

Received: September 16, 2015     Accepted: January 31, 2016     Published: February 22, 2016


Increasing evidences suggest several biological roles for erythropoietin and its receptor (Epo and EpoR), unrelated to erythropoiesis, including angiogenesis. Here, we detected the expression of EpoR in bone marrow-derived endothelial cells from monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM) patients (MGECs and MMECs, respectively) and assessed whether Epo plays a role in MGECs- and MMECs-mediated angiogenesis. We show that EpoR is expressed by both MGECs and MMECs even though at a higher level in the first ones. Both EC types respond to rHuEpo in terms of cell proliferation, whereas other responses, including activation of JAK2/STAT5 and PI3K/Akt pathways, cell migration and capillarogenesis are enhanced by Epo in MGECs, but not in MMECs. In addition, the conditioned media of both Epo-treated cells induce a strong angiogenic response in vivo in the chorioallantoic membrane assay, comparable to that of vascular endothelial growth factor (VEGF). Overall, these data highlight the effect of Epo on MGECs- and MMECs-mediated angiogenesis: MGECs are more responsive to Epo treatment than MMECs, probably because over-angiogenic phenotype of MMECs is already activated by their autocrine/paracrine loops occurring in the “angiogenic switch” from MGUS.

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