title: Bortezomib and zoledronic acid on angiogenic and vasculogenic activities of bone marrow macrophages in patients with multiple myeloma.
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-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.
authors.affiliation: Department of Internal Medicine and Clinical Oncology, University of Bari Medical School, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Moschetta
authors.forename: Giulia
authors.initials: G
authors.lastname: Di Pietro
authors.forename: Roberto
authors.initials: R
authors.lastname: Ria
authors.forename: Antonio
authors.initials: A
authors.lastname: Gnoni
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Mangialardi
authors.forename: Attilio
authors.initials: A
authors.lastname: Guarini
authors.forename: Paolo
authors.initials: P
authors.lastname: Ditonno
authors.forename: Pellegrino
authors.initials: P
authors.lastname: Musto
authors.forename: Fiorella
authors.initials: F
authors.lastname: D'Auria
authors.forename: Maria Rosaria
authors.initials: MR
authors.lastname: Ricciardi
authors.forename: Franco
authors.initials: F
authors.lastname: Dammacco
authors.forename: Domenico
authors.initials: D
authors.lastname: Ribatti
authors.forename: Angelo
authors.initials: A
authors.lastname: Vacca
mesh_terms: 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
chemical_list: 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