Vasculogenic mimicry by bone marrow macrophages in patients with multiple myeloma

C. Scavelli, B. Nico, T. Cirulli, R. Ria, G. Di Pietro, D. Mangieri, A. Bacigalupo, G. Mangialardi, A. M L Coluccia, T. Caravita, S. Molica, D. Ribatti, F. Dammacco, A. Vacca

Research output: Contribution to journalArticlepeer-review

Abstract

Bone marrow macrophages of patients with active and nonactive multiple myeloma (MM), monoclonal gammopathies of undetermined significance (MGUS) and benign anemia (controls) were stimulated for 7 days with vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), and analysed for the expression of endothelial cell (EC) markers by reverse transcription (RT)-PCR, real-time RT-PCR, western blot and immunofluorescence. Their vasculogenic ability was investigated in vitro in a Matrigel assay and in vivo on bone marrow biopsies through dual immunofluorescence and confocal laser microscopy. Active MM macrophages exposed to VEGF and bFGF acquired EC markers and formed capillary-like structures mimicking paired bone marrow ECs (multiple myeloma patient-derived endothelial cells, MMECs), with major responsiveness compared to macrophages from nonactive MM, MGUS or controls. Bone marrow biopsies of active MM harbored 'mosaic' vessels, being formed by MMECs, EC-like macrophages and macrophages themselves. These figures were rare in nonactive MM and absent in MGUS or controls. Our data indicate that macrophages contribute to build neovessels in active MM through vasculogenic mimicry, and this ability proceeds parallel to progression of the plasma cell tumors. Macrophages may be a target for the MM antivascular treatment.

Original languageEnglish
Pages (from-to)663-674
Number of pages12
JournalOncogene
Volume27
Issue number5
DOIs
Publication statusPublished - Jan 24 2008

Keywords

  • Basic fibroblast growth factor
  • Macrophages
  • Multiple myeloma
  • Vascular endothelial growth factor
  • Vasculogenesis

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

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