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Angiogenesis in multiple myeloma: correlation between in vitro endothelial colonies growth (CFU-En) and
M Dominici1, D Campioni, F Lanza
1Institute of Hematology, University of Ferrara, Italy.
Abstract:
Mouse models and studies performed on fixed bone marrow (BM) specimens obtained from patients with multiple myeloma (MM) suggest that plasma cell growth is dependent on endothelial cell (EC) proliferation within the BM microenvironment. In order to assess whether EC overgrowth in MM reflects a spontaneous in vitro angiogenesis, BM mononucleated cells from 13 untreated (UT) MM, 20 treated (11 with melphalan and nine with DAV schedule) MM, eight patients with monoclonal gammopathy of uncertain significance (MGUS) and eight controls were seeded in an unselective medium to assess EC proliferation. Furthermore, the influence of IL6 on the EC growth was investigated. Endothelial colonies (CFU-En) appeared as small clusters, formed by at least 100 slightly elongated and sometimes bi-nucleated cells expressing factor VIII, CD31 and CD105 (endoglin). The CFU-En mean number/10(6) BM mononucleated cells in untreated MM samples (2.07 s.d. +/- 1.3) was significantly higher than in normal BM (0.28 +/- 0.48), while no difference was seen between normal BM and MGUS (0.28 +/- 0.54). Interestingly, the mean number of CFU-En in the DAV group (1.88 +/- 1.6) did not differ from the UT, while it was found to be lower in the melphalan group (0.31 +/- 0.63). The addition of anti-IL6 monoclonal antibody induced a reduction of both the plasma cells in the supernatant and the CFU-En number. This study describes a rapid and feasible assay providing support for the association between EC and plasma cells further suggesting that the in vitro angiogenesis process may parallel that observed in vivo.
Insights
Multiple myeloma (MM) patients show increased endothelial cell (EC) proliferation, indicating spontaneous in vitro angiogenesis. Interleukin-6 (IL6) inhibition reduced both plasma cells and EC growth in bone marrow samples.
Area of Science:
- Hematology
- Oncology
- Cell Biology
Background:
- Bone marrow (BM) microenvironment plays a crucial role in plasma cell growth in multiple myeloma (MM).
- Previous studies suggest endothelial cell (EC) proliferation is linked to plasma cell growth in MM.
Purpose of the Study:
- To investigate whether EC overgrowth in MM reflects spontaneous in vitro angiogenesis.
- To assess the influence of Interleukin-6 (IL6) on EC proliferation in MM.
Main Methods:
- Bone marrow (BM) mononuclear cells from untreated MM, treated MM (melphalan, DAV schedule), monoclonal gammopathy of uncertain significance (MGUS), and control patients were cultured.
- Endothelial colony-forming units (CFU-En) were quantified to assess EC proliferation.
- The effect of anti-IL6 monoclonal antibody on plasma cells and CFU-En was evaluated.
Main Results:
- Significantly higher mean CFU-En numbers were observed in untreated MM patients compared to normal BM controls.
- No significant difference in CFU-En was found between normal BM and MGUS patients.
- The DAV treatment group showed similar CFU-En levels to untreated MM, while the melphalan group showed reduced CFU-En.
Conclusions:
- The study provides evidence for increased in vitro angiogenesis in multiple myeloma.
- EC proliferation is associated with plasma cell burden in MM.
- IL6 inhibition demonstrated a reduction in both plasma cells and EC growth, suggesting its role in MM angiogenesis.