title: Loss of inhibitory semaphorin 3A (SEMA3A) autocrine loops in bone marrow endothelial cells of patients with multiple myeloma.
abstract: 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.
authors: Department of Internal Medicine and Clinical Oncology, University of Bari Medical School, Bari, Italy. a.vacca@dimo.uniba.it
authors: Angelo
authors: A
authors: Vacca
authors: Claudio
authors: C
authors: Scavelli
authors: Guido
authors: G
authors: Serini
authors: Giulia
authors: G
authors: Di Pietro
authors: Teresa
authors: T
authors: Cirulli
authors: Francesca
authors: F
authors: Merchionne
authors: Domenico
authors: D
authors: Ribatti
authors: Federico
authors: F
authors: Bussolino
authors: Diego
authors: D
authors: Guidolin
authors: Giovanna
authors: G
authors: Piaggio
authors: Andrea
authors: A
authors: Bacigalupo
authors: Franco
authors: F
authors: Dammacco