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Upregulation of matrix metalloproteinase-9 in murine 5T33 multiple myeloma cells by interaction with bone marrow endothelial cells

Van Valckenborgh, Els; Bakkus, Marleen; Munaut, Carine; Noel, Agnes; St-Pierre, Yves ORCID logoORCID: https://orcid.org/0000-0002-1948-2041; Asosingh, Kewal; Van Riet, Ivan; Van Camp, Ben et Vanderkerken, Karen (2002). Upregulation of matrix metalloproteinase-9 in murine 5T33 multiple myeloma cells by interaction with bone marrow endothelial cells International Journal of Cancer , vol. 101 , nº 6. pp. 512-8. DOI: 10.1002/ijc.10642.

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Résumé


MM is a B-cell malignancy mainly characterized by monoclonal expansion of plasma cells in the BM, presence of paraprotein in serum and occurrence of osteolytic bone lesions. MMPs are a family of proteolytic enzymes that can contribute to cancer growth, invasion, angiogenesis, bone degradation and other processes important in the pathogenesis of MM. We investigated MMP-9 production in the 5T33MM murine model. Expression of MMP-9 protein in supernatant and cell extracts was analyzed by gelatin zymography. The in vitro, stroma-independent variant 5T33MMvt showed no protein expression of MMP-9 in contrast to in vivo growing MM cells, 5T33MMvv. However, when 5T33MMvt cells were injected into naive mice and isolated after tumor take (5T33MMvt-vv), they secreted a significant amount of MMP-9. These results were confirmed by specific staining of cytospins with an anti-MMP-9 antibody. The MMP-9 production by 5T33MMvt-vv cells disappeared when the cells were recultured in vitro. These data demonstrated that upregulation of MMP-9 occurs in vivo and that this process is dependent on the microenvironment. Cocultures of 5T33MMvt cells with STR10 BMECs induced MMP-9 in MM cells, as determined by both gelatin zymography and flow-cytometric analysis. In conclusion, our results demonstrate that MMP-9 production by MM cells is upregulated in vivo by the interaction of MM cells with BMECs.

Type de document: Article
Mots-clés libres: multiple myeloma; matrix metalloproteinase-9; bone marrow; stromal cell; endothelial cell
Centre: Centre INRS-Institut Armand Frappier
Date de dépôt: 07 mars 2025 21:45
Dernière modification: 07 mars 2025 21:45
URI: https://espace.inrs.ca/id/eprint/15245

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