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 an d tumor spreading. Multiple myeloma (MM) is a plasma cell malignancy primar ily localized within the bone marrow and characterized by its capacity to d estroy 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 hav e 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,,ve show that the soluble MMP, MMP-7, als o known as matrilysin, was able to activate the MMP-2 produced in its laten t form by bone marrow stromal cells. Finally, we demonstrate that myeloma c ells constitutively produce MMP-7 with expected proteolytic activity. Our r esults suggest that MMP-7 produced by myeloma cells could participate in bo ne destruction and tumor spreading in MM, on one hand by its own proteolyti c activity and on the other hand by its capacity to activate pro-MMP-2. The se findings strengthen the idea that inhibition of MMP activity could repre sent an interesting therapeutic approach in MM.