Multifunctional role of matrix metalloproteinases in multiple myeloma: a study in the 5T2MM mouse model.
Am J Pathol
; 165(3): 869-78, 2004 Sep.
Article
en En
| MEDLINE
| ID: mdl-15331411
ABSTRACT
Matrix metalloproteinases (MMPs) are known to play a role in cell growth, invasion, angiogenesis, metastasis, and bone degradation, all important events in the pathogenesis of cancer. Multiple myeloma is a B-cell cancer characterized by the proliferation of malignant plasma cells in the bone marrow, increased angiogenesis, and the development of osteolytic bone disease. The role of MMPs in the development of multiple myeloma is poorly understood. Using SC-964, a potent inhibitor of several MMPs (MMP-2, -3, -8, -9, and -13), we investigated the role of MMPs in the 5T2MM murine model. Reverse transcriptase-polymerase chain reaction demonstrated the presence of mRNA for MMP-2, -8, -9, and -13 in 5T2MM-diseased bone marrow. Mice bearing 5T2MM cells were given access to food containing SC-964. The concentration of SC-964 measured in the plasma of mice after 11 days of treatment was able to inhibit MMP-9 activity in gelatin zymography. Treatment of 5T2MM-bearing mice resulted in a significant reduction in tumor burden, a significant decrease in angiogenesis, and partially protective effect against the development of osteolytic bone disease. The direct role of MMPs in these different processes was confirmed by in vitro experiments. All these results support the multifunctional role of MMPs in the development of multiple myeloma.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Enfermedades Óseas
/
Metaloproteinasas de la Matriz
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Modelos Animales de Enfermedad
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Inhibidores Enzimáticos
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Mieloma Múltiple
Límite:
Animals
Idioma:
En
Revista:
Am J Pathol
Año:
2004
Tipo del documento:
Article
País de afiliación:
Bélgica