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DOI: 10.1160/TH04-06-0334
A VEGF-dependent autocrine loop mediates proliferation and capillarogenesis in bone marrow endothelial cells of patients with multiple myeloma
Financial support: Supported in part by Associazione Italiana per la Ricerca sul Cancro (AIRC), Milan, the Ministry for Education, the Universities and Research (Molecular Preclinical Therapy in Oncology – SP4 Funds, and Interuniversity Funds for Basic Research), Rome, and by a grant from Foundation Cassa di Risparmio di Puglia, Bari, Italy.
Publication History
Received
01 June 2004
Accepted after resubmission
28 September 2004
Publication Date:
04 December 2017 (online)
Summary
The expression/function of vascular endothelial growth factor (VEGF) and its receptor 2 (VEGFR-2/KDR) in multiple myeloma (MM)-associated angiogenesis is under scrutiny. We show here that bone marrow endothelial cells (EC) from 16 patients with MM (MMEC) highly expressed VEGF-A (the main VEGF isoform) and VEGFR-2 at both mRNA and protein level, whereas EC from 14 patients with monoclonal gammopathy unassociated/unattributable (MG[u]) (MG[u]EC) and 12 human umbilical veins (HUVEC) expressed very low mRNAs and/or proteins. MMEC showed constitutive autophosphorylation in both VEGFR-2 and the associated extracellular signal-regulated kinase-2 (ERK-2), whereas this was marginal in MG[u]EC and HUVEC. MMEC proliferated rapidly and formed a closely-knit capillary meshwork on Matrigel. These cell functions were reduced in the other EC. Autophosphorylation, proliferation and capillarogenesis were prevented by a neutralizing antiVEGF-A antibody, and more efficaciously by an anti-VEGFR-2 antibody. Both antibodies had no effect or were poorly effective on the other EC. These findings as a whole suggest the existence of an autocrine loop of VEGF in MMEC. Since this is very likely a mechanism for the amplification of VEGF activity in neovascularization, it would constitute an appropriate target for antiangiogenic management in MM.
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