Loss of inhibitory semaphorin 3A (SEMA3A) autocrine loops in bone marrow endothelial cells of patients with multiple myeloma
Copyright policy )Loss of inhibitory semaphorin 3A (SEMA3A) autocrine loops in bone marrow endothelial cells of patients with multiple myeloma
Vascular endothelial growth factor165 (VEGF165) and semaphorin3A (SEMA3A) elicit pro- and antiangiogenic signals respectively in endothelial cells (ECs) by binding to their receptors VEGFR-2, neuropilin-1 (NRP1), and plexin-A1. Here we show that the VEGF165-driven angiogenic potential of multiple myeloma (MM) ECs is significantly higher than that of monoclonal gammopathy of undetermined significance (MGUS) ECs (MGECs) and human umbilical vein (HUV) ECs. This is probably due to a constitutive imbalance of endogenous VEGF165/SEMA3A ratio, which leans on VEGF165 in MMECs but on SEMA3A in MGECs and HUVECs. Exogenous VEGF165 induces SEMA3A expression in MGECs and HUVECs, but not in MMECs. Moreover, by counteracting VEGF165 activity as efficiently as an anti-VEGFR-2 antibody, exogenous SEMA3A restrains the over-angiogenic potential of MMECs. Our data indicate that loss of endothelial SEMA3A in favor of VEGF165 could be responsible for the angiogenic switch from MGUS to MM.
- University of Turin Italy
- University of Bari Aldo Moro Italy
- University of Padua Italy
Vascular Endothelial Growth Factor A, Reverse Transcriptase Polymerase Chain Reaction, Chemotaxis, Endothelial Cells, Neovascularization, Physiologic, Bone Marrow Cells, Semaphorin-3A, Receptors, Vascular Endothelial Growth Factor, Humans, Multiple Myeloma, Cell Division, Cells, Cultured, DNA Primers
Vascular Endothelial Growth Factor A, Reverse Transcriptase Polymerase Chain Reaction, Chemotaxis, Endothelial Cells, Neovascularization, Physiologic, Bone Marrow Cells, Semaphorin-3A, Receptors, Vascular Endothelial Growth Factor, Humans, Multiple Myeloma, Cell Division, Cells, Cultured, DNA Primers
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