Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.23 (MMP)
 4,246 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Membrane-type metalloproteinase-I (MTI-MMP) is a transmembrane metalloproteinase, which activates pro-gelatinase A. There has been disagreement as to whether the cell types expressing MTI-MMP are cancer cells or stromal fibroblasts. Using human gastrointestinal carcinomas, the present study disclosed the tissue localization of MTI-MMP mRNA by in situ hybridization and ultrastructural localization of its protein by immunoelectron microscopy. In normal colon and stomach tissues, MTI-MMP mRNA and protein were negative or faintly positive both in epithelial cells and in stromal fibroblasts, except in the fundic gland of the stomach, which showed the positivity for MTI-MMP. In contrast, gastrointestinal cancer tissue showed over-expression of MTI-MMP mRNA and protein both in cancer cells and in stromal cells (fibroblasts). Stromal fibroblasts also expressed mRNA for gelatinase A and type-I procollagen. Double immunohistochemistry revealed that macrophages were also positive for MTI-MMP. Immunoelectron microscopy showed that MTI-MMP was localized along the plasma membrane of cancer cells and macrophages and in rough endoplasmic reticulum of fibroblasts. The present study reveals a dual over-expression pattern of MTI-MMP both in cancer cells and in stromal fibroblasts; the expression in cancer cells may be related to the invasive growth, whereas that in fibroblasts may be related to the tissue remodeling process caused by invasive growth of cancer cells.
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PMID:Dual over-expression pattern of membrane-type metalloproteinase-1 in cancer and stromal cells in human gastrointestinal carcinoma revealed by in situ hybridization and immunoelectron microscopy. 893 35

Toll-like receptor 9 (TLR9) recognizes both bacterial and self-DNA and it is abundantly expressed in the gastrointestinal tract. In this study, we investigated the influences of both bacterial DNA and specific short DNA sequences on TLR9-mediated gastrointestinal cancer cell invasion. We assessed the effect of various DNA ligands on cellular invasion and on TLR9 and matrix metalloproteinase expression of three gastrointestinal cancer cell lines. DNA-ligands described in this study include CpG-ODN M362, 9-mer (hairpin), human telomeric sequence h-Tel22 G-quadruplex, and bacterial DNAs from Escherichia coli and Helicobacter pylori. All of the DNAs studied were demonstrated to induce invasion in the studied cells. The DNA-induced invasion was inhibited with a broad-spectrum MMP inhibitor and partly also with chloroquine suggesting that it could be mediated via MMP activation, endosomal signaling, and TLR9. Interestingly, H. pylori DNA was shown to induce a more pronounced invasion in a gastric cancer cell line than in the other cell lines. Our results suggest that bacterial DNA as well as deoxynucleotides having stable secondary structures (i.e. hairpins or G-quadruplex structures) may serve as endogenous, invasion-inducing TLR9-ligands and promote local progression and metastasis of cancers in the alimentary tract.
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PMID:Short DNA sequences and bacterial DNA induce esophageal, gastric, and colorectal cancer cell invasion. 2308 43