Bone marrow angiogenesis and progression in multiple myeloma.
Roberto Ria1, Antonia Reale, Annunziata De Luisi
1Department of Biomedical Sciences and Human Oncology, Section of Internal Medicine and Clinical Oncology, University of Bari "Aldo Moro" Medical School Bari, Italy.
American Journal of Blood Research
|March 21, 2012
Summary
Multiple myeloma plasma cells drive abnormal bone remodeling and tumor growth by promoting neovascularization. These cancer cells recruit other cells, like macrophages, to secrete factors that stimulate new blood vessel formation, aiding disease progression.
Area of Science:
- Oncology
- Hematology
- Cell Biology
Background:
- Multiple myeloma (MM) is characterized by plasma cell accumulation in the bone marrow, leading to bone destruction.
- Neovascularization is a critical process in MM progression, contributing to tumor growth and survival.
- The bone marrow microenvironment plays a significant role in MM pathogenesis, influencing tumor cell behavior and disease advancement.
Purpose of the Study:
- To elucidate the mechanisms by which multiple myeloma plasma cells induce neovascularization and vasculogenesis in the bone marrow microenvironment.
- To investigate the role of cytokines and stromal cell interactions in promoting angiogenesis and vascular formation in MM.
- To understand how myeloma cells recruit and activate stromal cells, such as macrophages, to contribute to tumor vascularization.
Main Methods:
- Analysis of interactions between myeloma plasma cells and the bone marrow microenvironment.
- Investigation of cytokine signaling pathways, including interleukin-6 (IL-6) and chemokines (e.g., IL-8, ITAC, Mig, IP-10).
- Assessment of the role of angiogenic factors (e.g., VEGF, FGF-2) and their impact on endothelial cell differentiation and macrophage behavior.
Main Results:
- Myeloma plasma cells secrete factors like vascular endothelial growth factor (VEGF) and fibroblast growth factor-2 (FGF-2) that promote neovascularization.
- Interactions between plasma cells and stromal cells, particularly via IL-6, stimulate the release of angiogenic factors from other bone marrow cells.
- Myeloma cells recruit and activate macrophages and mast cells, which in turn secrete additional angiogenic factors, enhancing tumor vascularization.
- Activated myeloma-associated macrophages can exhibit vasculogenic properties, differentiating into cells resembling endothelial cells and contributing to vascular mimicry.
Conclusions:
- Multiple myeloma plasma cells orchestrate a complex process of neovascularization and vasculogenesis within the bone marrow.
- The interplay between myeloma cells, cytokines, and stromal cells is crucial for driving tumor angiogenesis and disease progression.
- Targeting these intricate microenvironmental interactions presents potential therapeutic strategies for multiple myeloma.
Keywords:
Angiogenesisendothelial cellsfibroblast growth factor-2multiple myelomatumor progressionvascular endothelial growth factorvasculogenesisMore Related Videos
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