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- W2034995181 abstract "Abstract It is now recognized that the extracellular matrix (ECM) of bone marrow (BM) plays a role not only in supporting BM structure but also in regulating cellular functions. Matrix metalloproteinases (MMPs) and their nature tissue inhibitors (TIMPs) regulate ECM turnover and TIMPs also regulate cell growth. As human long-term bone marrow culture (LTMC) mimics the hematopoietic microenvironment, we used this model to examine the secretion of MMPs and TIMPs. To evaluate the contribution of individual lineages we examined the expression of MMP-2, MMP-9, MT-1 MMP, MT-4 MMP and TIMPs-1, -2 and -3 by hematopoietic cells of erythroid, myeloid and megakaryocytic lineages (expanded in vitro from human normal BM CD34 + cells) and by BM stromal cells (CFU-F, endothelial cells). We found that MMP-9 is expressed and secreted by precursors of all hematopoietic lineages while MMP-2 and MT-1 MMP are expressed mainly by stromal cells and cells of myeloid and megakaryocytic but not erythroid lineages. BM stromal cells expressed and secreted high levels of all the TIMPs tested. This pattern of secretion of MMPs and TIMPs was reflected in the LTMC system: during the first week of LTMC MMP-9 levels were high and then decreased with reduced number of hematopoietic cells while levels of MMP-2, TIMP-1 and TIMP-2 increased with establishment of an adherent layer and expansion of stromal cells. TIMP-3 was released from the ECM matrix by the end of week 8–9 when the production of CFU-GM by adherent and nonadherent layers decreased significantly. Thus we present clear evidence that MMPs and TIMPs are constituents of the hematopoietic microenvironment and we are now investigating their role in hematopoiesis." @default.
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- W2034995181 date "2000-07-01" @default.
- W2034995181 modified "2023-10-18" @default.
- W2034995181 title "Evaluation of mmp and timp expression in the hematopoietic microenvironment" @default.
- W2034995181 doi "https://doi.org/10.1016/s0301-472x(00)00372-6" @default.
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