Vasculogenic mimicry by bone marrow macrophages in patients with multiple myeloma.
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.
Department of Internal Medicine and Clinical Oncology, University of Bari Medical School, Bari, Italy.
C
C
Scavelli
B
B
Nico
T
T
Cirulli
R
R
Ria
G
G
Di Pietro
D
D
Mangieri
A
A
Bacigalupo
G
G
Mangialardi
A M L
AM
Coluccia
T
T
Caravita
S
S
Molica
D
D
Ribatti
F
F
Dammacco
A
A
Vacca
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000740:Anemia / Q000503:physiopathology; D001854:Bone Marrow Cells; D016022:Case-Control Studies; D018929:Cell Culture Techniques; D018450:Disease Progression; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000502:physiology; D006801:Humans; D008264:Macrophages / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000503:physiopathology*; D009389:Neovascularization, Pathologic; D010265:Paraproteinemias / Q000503:physiopathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology
D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2