The role of metalloproteinases and their inhibitors in hematological disorders.
The balance between the activities of matrix metalloproteinases (MMPs) and the tissue inhibitors of metalloproteinases (TIMPs) is an important control point during the turnover of the extracellular matrix. Previous studies have demonstrated that an uncontrolled rate of production of these proteins leads to various pathological conditions. Overexpression of MMPs by malignant cells can increase the invasive behavior of solid tumors and their metastatic potential. In an increasing number of reports, it has become evident that expression of MMPs and TIMPs is not restricted to solid tumors. Normal and malignant hematological cells also express these proteins and play a pivotal role in the hematological-cell physiology. In addition to modifying the extracellular matrix, MMPs and TIMPs exert other functions in hematological cells, including growth-factor activity, removal of cell-surface receptors, and autoimmunity. The goal of this review is to gather recent studies concerning the properties of MMPs and TIMPs in hematological cells, their regulation of gene expression, their cellular distribution, and their potential role in the pathogenesis of hematological disorders such as inflammation and neoplasia.
Guedez
L
L
Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-1500, USA.
Lim
M S
MS
Stetler-Stevenson
W G
WG
D000818:Animals; D016207:Cytokines / Q000378:metabolism; D006402:Hematologic Diseases / Q000235:genetics / Q000378:metabolism*; D019337:Hematologic Neoplasms / Q000235:genetics / Q000378:metabolism; D006410:Hematopoiesis / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D007962:Leukocytes / Q000201:enzymology; D008214:Lymphocytes / Q000378:metabolism / Q000473:pathology; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors* / Q000145:classification / Q000502:physiology*; D011480:Protease Inhibitors / Q000145:classification / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism
D016207:Cytokines; D011480:Protease Inhibitors; D011956:Receptors, Cell Surface; D008666:Metalloendopeptidases