The concept of tumor suppression by tissue inhibitor of metalloproteinases (TIMPs) has evolved primarily from studies of genetically modulated tumor cells. The next step is to focus on the host and assess the protective potential of host TIMP-1 on primary tumor growth and metastasis. We generated two transgenic mouse lines with altered Timp-1 expression in skin and liver: one overexpressed Timp...

Matrix metalloproteinases (MMPs) and their endogenous inhibitors (TIMPs) regulate epithelial-mesenchymal transition (EMT) critical for the development of epithelial organs as well as cancer cell invasion. TIMP-1 is frequently overexpressed in several types of human cancers and serves as a prognostic marker. The present study investigates the roles of TIMP-1 on the EMT process and formation of t...

Atherosclerotic plaque stability depends on the structural integrity of its extracellular matrix skeleton. The balance between degradation by matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) may regulate plaque stability. Although MMP expression in atheroma is well documented, localization and control of expression of TIMPs in these lesions is incomplete. Ext...

Tissue inhibitors of metalloproteinases (TIMPs) have been shown to be multifunctional factors. Contrasting with their enzyme-inhibitory activity, TIMPs also promote cell growth. Previously, we have reported an enhanced expression of TIMP-1 by normal reactive B cells and high-grade lymphomas. In the present study, a series of Burkitt's lymphoma (BL) cell lines were analyzed for their expression ...

To test the hypothesis that Helicobacter pylori regulates gastric cell secretion of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs), culture media from infected and uninfected human gastric adenocarcinoma (AGS) cells were analyzed by zymography, MMP activity assays, and immunoblotting. AGS cells secreted gelatinolytic (prominently 90 kDa) and caseinolytic (1...

The objective of the present study was to measure preoperative plasma tissue inhibitor of metalloproteinase (TIMP)-1 levels in colorectal cancer patients and relate these values to clinical and biochemical patient characteristics. TIMP-1 levels were determined by ELISA in EDTA plasma samples collected preoperatively from 588 colorectal cancer patients. Plasma TIMP-1 levels were distributed with...

OBJECTIVE An excess of metalloproteinases (MMPs) over tissue inhibitors of metalloproteinases (TIMPs) may favor atherosclerotic plaque rupture. We compared TIMP levels in nonfoamy and foam-cell macrophages (FCM) generated in vivo. METHODS AND RESULTS In vivo generated rabbit FCM exhibited 84% reduced TIMP-3 protein compared to nonfoamy macrophages, and immunocytochemistry revealed a TIMP-3 ne...

Recently matrix metalloproteinase-9 (MMP-9) and its endogenous inhibitor (tissue inhibitor of metalloproteinase-1, TIMP-1) have been implicated in complicated malaria. In vivo, mice with cerebral malaria (CM) display high levels of both MMP-9 and TIMP-1, and in human patients TIMP-1 serum levels directly correlate with disease severity. In vitro, natural haemozoin (nHZ, malarial pigment) enhanc...

BACKGROUND Matrix Metalloproteinase functions in the remodeling of the extracellular matrix that is integral for many normal and pathological processes such as morphogenesis, angiogenesis, tissue repair, and tumor invasion. The tissue inhibitor of the metalloproteinase family including the tissue inhibitor of metalloproteinase-2 (TIMP-2) regulates the activity of multifunctional metalloproteina...

The antiangiogenic function of the tissue inhibitors of metalloproteinases (TIMPs) has been attributed to their matrix metalloproteinase inhibitory activity. Here we demonstrate that TIMP-1 but not Ala+TIMP-1 inhibits both basal and vascular endothelial growth factor (VEGF)-stimulated migration of human microvascular endothelial cells (hMVECs), suggesting that this effect is dependent on direct...