Production of metalloproteinase-7 (matrilysin) by human myeloma cells and its potential involvement in metalloproteinase-2 activation.
Matrix metalloproteinases (MMPs) play a critical role in bone remodeling and tumor spreading. Multiple myeloma (MM) is a plasma cell malignancy primarily localized within the bone marrow and characterized by its capacity to destroy bone matrix and to disseminate. We have reported recently that human myeloma cells were able to induce the conversion of pro-MMP-2 produced by the tumoral environment in its activated form. In the current study, we have investigated the mechanism involved in this process. We demonstrate that a soluble MMP constitutively produced by myeloma cells was responsible for pro-MMP-2 activation. Furthermore, we show that the soluble MMP, MMP-7, also known as matrilysin, was able to activate the MMP-2 produced in its latent form by bone marrow stromal cells. Finally, we demonstrate that myeloma cells constitutively produce MMP-7 with expected proteolytic activity. Our results suggest that MMP-7 produced by myeloma cells could participate in bone destruction and tumor spreading in MM, on one hand by its own proteolytic activity and on the other hand by its capacity to activate pro-MMP-2. These findings strengthen the idea that inhibition of MMP activity could represent an interesting therapeutic approach in MM.
Barillé
S
S
Institut National de la Santé et de la Recherche Médicale U463, Institut de Biologie, Nantes, France. sbarille@nantes.inserm.fr
Bataille
R
R
Rapp
M J
MJ
Harousseau
J L
JL
Amiot
M
M
D001854:Bone Marrow Cells / Q000201:enzymology; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000378:metabolism; D010450:Endopeptidases / Q000378:metabolism; D004789:Enzyme Activation; D004792:Enzyme Precursors / Q000378:metabolism; D018093:Gelatinases / Q000378:metabolism; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020783:Matrix Metalloproteinase 7 / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology*; D008666:Metalloendopeptidases / Q000378:metabolism; D009101:Multiple Myeloma / Q000201:enzymology* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D012995:Solubility; D017154:Stromal Cells / Q000201:enzymology; D014407:Tumor Cells, Cultured
D017077:Culture Media, Conditioned; D004792:Enzyme Precursors; D012333:RNA, Messenger; D010450:Endopeptidases; D018093:Gelatinases; D008666:Metalloendopeptidases; C069860:progelatinase; D020783:Matrix Metalloproteinase 7; D020778:Matrix Metalloproteinase 2