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Volume 46, Issue 2, Pages 420-429 (January 2010)


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Bortezomib and zoledronic acid on angiogenic and vasculogenic activities of bone marrow macrophages in patients with multiple myeloma

Michele Moschettaa, Giulia Di Pietroa, Roberto Riaa, Antonio Gnonia, Giuseppe Mangialardia, Attilio Guarinib, Paolo Ditonnoc, Pellegrino Mustod, Fiorella D’Auriad, Maria Rosaria Ricciardie, Franco Dammaccoa, Domenico Ribattif, Angelo VaccaaCorresponding Author Informationemail address

Received 28 July 2009; accepted 15 October 2009. published online 16 November 2009.

Abstract 

Bone marrow neovascularisation supports plasma cell tumour progression in patients with multiple myeloma (MM), and is partially sustained by bone marrow macrophages through their angiogenic and vasculogenic activities. As such, macrophages may be a target for antivascular treatment in MM. Here, we show that bortezomib (BZ) and zoledronic acid (ZOL) display distinct and synergistic inhibitory effects on cell proliferation, adhesion, migration and expression of angiogenic cytokines (i.e.: VEGF, bFGF, HGF and PDGF). Similar effects were found on capillarogenic organisation and expression of vascular markers in cells which became vasculogenic. VEGFR2 and ERK1/2 phosphoactivation as well as NF-κB activity were also inhibited. Overall these data provide evidence that the exposure of bone marrow macrophages in MM during the treatment with ZOL and BZ, alone and or in combination, impacts their angiogenic and vasculogenic properties, suggesting that these cells may be considered as a target of both drugs in MM patients.

a Department of Internal Medicine and Clinical Oncology, University of Bari Medical School, Italy

b Hematology Unit, Institute of Oncology ‘Giovanni Paolo II’, I-70100 Bari, Italy

c Hematology Unit, ‘Di Venere’ Hospital, I-74100 Bari, Italy

d Hematology and Bone Marrow Transplantation Unit, Centro di Riferimento Oncologico della Basilicata IRCCS-CROB, I-85028 Rionero in Vulture, Potenza, Italy

e Division of Hematology, Department of Cellular Biotechnologies and Hematology, University ‘La Sapienza’, I-00100 Rome, Italy

f Department of Human Anatomy and Histology, University of Bari Medical School, Italy

Corresponding Author InformationCorresponding author: Department of Internal Medicine and Clinical Oncology, Policlinico – Piazza Giulio Cesare, 11, I-70124 Bari, Italy. Tel.: +39 080 559 34 44; fax: +39 080 559 21 89.

PII: S0959-8049(09)00777-1

doi:10.1016/j.ejca.2009.10.019


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