Send to

Choose Destination
Thromb Haemost. 2004 Dec;92(6):1438-45.

A VEGF-dependent autocrine loop mediates proliferation and capillarogenesis in bone marrow endothelial cells of patients with multiple myeloma.

Author information

Department of Internal Medicine and Clinical Oncology, Piazza Giulio Cesare, 11, Policlinico, I-70124, Bari, Italy.

Erratum in

  • Thromb Haemost. 2005 Feb;93(2):397.


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 anti-VEGF-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.

[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Georg Thieme Verlag Stuttgart, New York
Loading ...
Support Center