Increasing evidences suggest several biological roles for erythropoietin and its receptor (Epo an... more 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). O...
Purpose: To investigate the angiogenic role of the HGF/cMET pathway and its inhibition in bone ma... more Purpose: To investigate the angiogenic role of the HGF/cMET pathway and its inhibition in bone marrow (BM) endothelial cells (ECs) from patients with multiple myeloma (MM) vs those with monoclonal gammopathy of undetermined significance (MGUS) or benign anemia (controls). Experimental Design: The HGF/cMET pathway was evaluated in ECs from MM patients (MMECs) at diagnosis, at relapse after bortezomib- or lenalidomide-based therapies or on refractory phase to these drugs, in ECs from patients with MGUS (MGECs), and in those from controls. The effects of a selective cMET tyrosine kinase inhibitor (SU11274) on the MMECs angiogenic activities were studied in vitro and in vivo. Results: MMECs express more HGF, cMET, and activated cMET (phospho (p)-cMET) at both RNA and protein level vs MGECs and control ECs. MMECs are able to maintain the HGF/cMET pathway activation in absence of external stimulation, while treatment with anti-HGF and anti-cMET neutralizing antibodies (Abs) is able to inh...
To determine the in vivo and in vitro antiangiogenic power of lenalidomide, a &am... more To determine the in vivo and in vitro antiangiogenic power of lenalidomide, a "lead compound" of IMiD immunomodulatory drugs in bone marrow (BM) endothelial cells (EC) of patients with multiple myeloma (MM) in active phase (MMEC).
Increasing evidences suggest several biological roles for erythropoietin and its receptor (Epo an... more 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). O...
Purpose: To investigate the angiogenic role of the HGF/cMET pathway and its inhibition in bone ma... more Purpose: To investigate the angiogenic role of the HGF/cMET pathway and its inhibition in bone marrow (BM) endothelial cells (ECs) from patients with multiple myeloma (MM) vs those with monoclonal gammopathy of undetermined significance (MGUS) or benign anemia (controls). Experimental Design: The HGF/cMET pathway was evaluated in ECs from MM patients (MMECs) at diagnosis, at relapse after bortezomib- or lenalidomide-based therapies or on refractory phase to these drugs, in ECs from patients with MGUS (MGECs), and in those from controls. The effects of a selective cMET tyrosine kinase inhibitor (SU11274) on the MMECs angiogenic activities were studied in vitro and in vivo. Results: MMECs express more HGF, cMET, and activated cMET (phospho (p)-cMET) at both RNA and protein level vs MGECs and control ECs. MMECs are able to maintain the HGF/cMET pathway activation in absence of external stimulation, while treatment with anti-HGF and anti-cMET neutralizing antibodies (Abs) is able to inh...
To determine the in vivo and in vitro antiangiogenic power of lenalidomide, a &am... more To determine the in vivo and in vitro antiangiogenic power of lenalidomide, a "lead compound" of IMiD immunomodulatory drugs in bone marrow (BM) endothelial cells (EC) of patients with multiple myeloma (MM) in active phase (MMEC).
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Papers by Arianna Ferrucci