Vasculogenic mimicry by bone marrow macrophages in patients with multiple myeloma
- 30 July 2007
- journal article
- research article
- Published by Springer Science and Business Media LLC in Oncogene
- Vol. 27 (5), 663-674
- https://doi.org/10.1038/sj.onc.1210691
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.Keywords
This publication has 37 references indexed in Scilit:
- Decreased Macrophage Number and Activation Lead to Reduced Lymphatic Vessel Formation and Contribute to Impaired Diabetic Wound HealingThe American Journal of Pathology, 2007
- Alternative Vascularization Mechanisms in Cancer: Pathology and Therapeutic ImplicationsThe American Journal of Pathology, 2007
- Endothelial cadherins and tumor angiogenesisExperimental Cell Research, 2006
- Circulating endothelial progenitor cells in multiple myeloma: implications and significanceBlood, 2005
- Functional Adaptation: The Key to Plasticity of Cardiovascular "Stem" Cells?Stem Cells and Development, 2005
- A new image analysis method based on topological and fractal parameters to evaluate the angiostatic activity of docetaxel by using the Matrigel assay in vitroMicrovascular Research, 2003
- Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT MethodMethods, 2001
- Vascular Channel Formation by Human Melanoma Cells in Vivo and in Vitro: Vasculogenic MimicryThe American Journal of Pathology, 1999
- Role of the Flt-1 receptor tyrosine kinase in regulating the assembly of vascular endotheliumNature, 1995
- Potent synergism between vascular endothelial growth factor and basic fibroblast growth factor in the induction of angiogenesis in vitroBiochemical and Biophysical Research Communications, 1992