Bortezomib and zoledronic acid on angiogenic and vasculogenic activities of bone marrow macrophages in patients with multiple myeloma.
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-kappaB 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.
Moschetta
Michele
M
Department of Internal Medicine and Clinical Oncology, University of Bari Medical School, Italy.
Di Pietro
Giulia
G
Ria
Roberto
R
Gnoni
Antonio
A
Mangialardi
Giuseppe
G
Guarini
Attilio
A
Ditonno
Paolo
P
Musto
Pellegrino
P
D'Auria
Fiorella
F
Ricciardi
Maria Rosaria
MR
Dammacco
Franco
F
Ribatti
Domenico
D
Vacca
Angelo
A
D000368:Aged; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism; D001897:Boronic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D000069286:Bortezomib; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004164:Diphosphonates / Q000008:administration & dosage / Q000494:pharmacology*; D004357:Drug Synergism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000098:blood supply / Q000188:drug therapy*; D016328:NF-kappa B / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D010766:Phosphorylation; D011719:Pyrazines / Q000008:administration & dosage / Q000494:pharmacology*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism; D000077211:Zoledronic Acid
D020533:Angiogenesis Inhibitors; D014408:Biomarkers, Tumor; D001897:Boronic Acids; D004164:Diphosphonates; D007093:Imidazoles; D016328:NF-kappa B; D011719:Pyrazines; D000069286:Bortezomib; D000077211:Zoledronic Acid; D040301:Vascular Endothelial Growth Factor Receptor-2; D048049:Extracellular Signal-Regulated MAP Kinases