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-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.