Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 14510-14521 |
| Number of pages | 12 |
| Journal | Oncotarget |
| Volume | 7 |
| Issue number | 12 |
| DOIs | |
| Publication status | Published - Mar 22 2016 |
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Keywords
- Angiogenesis
- Endothelial cells
- Erythropoietin
- Monoclonal gammopathy of undetermined significance
- Multiple myeloma
ASJC Scopus subject areas
- Oncology
Cite this
Role of erythropoietin in the angiogenic activity of bone marrow endothelial cells of MGUS and multiple myeloma patients. / Lamanuzzi, Aurelia; Saltarella, Ilaria; Ferrucci, Arianna; Ria, Roberto; Ruggieri, Simona; Racanelli, Vito; Rao, Luigia; Annese, Tiziana; Nico, Beatrice; Vacca, Angelo; Ribatti, Domenico.
In: Oncotarget, Vol. 7, No. 12, 22.03.2016, p. 14510-14521.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Role of erythropoietin in the angiogenic activity of bone marrow endothelial cells of MGUS and multiple myeloma patients
AU - Lamanuzzi, Aurelia
AU - Saltarella, Ilaria
AU - Ferrucci, Arianna
AU - Ria, Roberto
AU - Ruggieri, Simona
AU - Racanelli, Vito
AU - Rao, Luigia
AU - Annese, Tiziana
AU - Nico, Beatrice
AU - Vacca, Angelo
AU - Ribatti, Domenico
PY - 2016/3/22
Y1 - 2016/3/22
N2 - 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.
AB - 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.
KW - Angiogenesis
KW - Endothelial cells
KW - Erythropoietin
KW - Monoclonal gammopathy of undetermined significance
KW - Multiple myeloma
UR - http://www.scopus.com/inward/record.url?scp=84971607216&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84971607216&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.7587
DO - 10.18632/oncotarget.7587
M3 - Article
VL - 7
SP - 14510
EP - 14521
JO - Oncotarget
JF - Oncotarget
SN - 1949-2553
IS - 12
ER -