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Adhesive interactions between tumour cells and bone marrow stromal elements in human multiple myeloma
L Faid1, I Van Riet, M De Waele
1Department of Hematology and Immunology, Free University Brussels (VUB), Belgium.
European Journal of Haematology
|November 1, 1996
Summary
This study reveals that myeloma bone marrow stroma has increased macrophages and osteoclasts, with plasma cells expressing specific adhesion molecules. Myeloma cells bind strongly to stroma and fibronectin, but unknown mechanisms mediate this binding, suggesting novel therapeutic targets.
Area of Science:
- Hematology
- Cell Biology
- Immunology
Background:
- Multiple myeloma is a hematological malignancy characterized by the proliferation of plasma cells in the bone marrow.
- The bone marrow microenvironment plays a critical role in myeloma progression and pathogenesis.
- Understanding the interactions between myeloma cells and the bone marrow stroma is crucial for developing effective therapies.
Purpose of the Study:
- To investigate the characteristics of bone marrow stroma in multiple myeloma patients.
- To analyze the expression of adhesion molecules on myeloma cells and bone marrow stromal cells.
- To elucidate the adhesive interactions between myeloma cells and the bone marrow microenvironment.
Main Methods:
- Establishment of long-term bone marrow cultures (LTBMC) from myeloma patients and healthy donors.
- In situ immunogold-silver staining for analyzing cell populations and adhesion molecule expression.
- Assessment of myeloma cell adhesion to bone marrow stromal layers and purified ligands using cell lines.
Main Results:
- Myeloma LTBMC exhibited reduced stromal confluency and an increased proportion of macrophages and osteoclasts compared to normal LTBMC.
- Myeloma plasma cells expressed VLA-4, H-CAM, ICAM-1, and N-CAM, while stromal fibroblasts showed strong expression of VCAM-1, H-CAM, and ICAM-1.
- Myeloma cell lines demonstrated strong binding to stromal layers and fibronectin, but this adhesion was not significantly inhibited by antibodies targeting known adhesion molecules and their receptors.
Conclusions:
- The bone marrow microenvironment in multiple myeloma is altered, with changes in stromal composition and increased inflammatory cells.
- Myeloma cells express adhesion molecules that can interact with ligands on stromal cells, but these interactions do not fully explain myeloma cell adhesion.
- The study suggests the involvement of unidentified mechanisms in mediating myeloma cell binding to the bone marrow microenvironment, highlighting potential new therapeutic avenues.