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

Michele Moschetta, Giulia Di Pietro, Roberto Ria, Antonio Gnoni, Giuseppe Mangialardi, Attilio Guarini, Paolo Ditonno, Pellegrino Musto, Fiorella D'Auria, Maria Rosaria Ricciardi, Franco Dammacco, Domenico Ribatti, Angelo Vacca

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)420-429
Number of pages10
JournalEuropean Journal of Cancer
Volume46
Issue number2
DOIs
Publication statusPublished - Jan 2010

Keywords

  • Angiogenesis
  • Bortezomib
  • Macrophages
  • Multiple myeloma
  • Vasculogenesis
  • Zoledronic acid

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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  • Cite this

    Moschetta, M., Di Pietro, G., Ria, R., Gnoni, A., Mangialardi, G., Guarini, A., Ditonno, P., Musto, P., D'Auria, F., Ricciardi, M. R., Dammacco, F., Ribatti, D., & Vacca, A. (2010). Bortezomib and zoledronic acid on angiogenic and vasculogenic activities of bone marrow macrophages in patients with multiple myeloma. European Journal of Cancer, 46(2), 420-429. https://doi.org/10.1016/j.ejca.2009.10.019