Bone marrow angiogenesis in patients with active multiple myeloma

Area of Science:

• Hematology
• Oncology
• Vascular Biology

Background:

• Multiple myeloma (MM) is a plasma cell malignancy.
• The role of angiogenesis in active MM progression is not fully understood.
• Understanding the vascular phase is crucial for MM treatment.

Purpose of the Study:

• To investigate microvessel density and angiogenic factors in active MM.
• To explore the role of fibroblast growth factor-2 (FGF-2) and matrix metalloproteinase-2 (MMP-2) in MM angiogenesis.
• To assess the contribution of mast cells to the vascular phase of MM.

Main Methods:

• Immunohistochemistry and computerized image analysis for microvessel area (FVIII-RA, AQP1).
• In vitro assays using conditioned medium (CM) from plasma cells.
• Chick embryo chorioallantoic membrane (CAM) assay for in vivo angiogenesis.
• Immunoassay for FGF-2, in situ hybridization for MMP-2 mRNA, and zymography for MMP-2 protein.

Main Results:

• Active MM patients showed significantly increased FVIII-RA and AQP1 microvessel areas compared to non-active MM and MGUS.
• CM from active MM plasma cells strongly stimulated endothelial and monocyte chemotaxis and angiogenesis.
• Higher FGF-2 levels were found in active MM, and anti-FGF-2 antibodies inhibited CM activity.
• Active MM patients exhibited higher MMP-2 mRNA and protein expression.

Conclusions:

• Active MM represents a vascular phase characterized by increased angiogenesis, partly mediated by FGF-2 and MMP-2.
• Mast cells may contribute to angiogenesis in MM.
• Angiogenesis and MMP-2 secretion likely facilitate tumor cell dissemination in active MM.