Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.3 (collagenase)
 18,340 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tissue factor pathway inhibitor-2 (TFPI-2)/matrix-associated serine protease inhibitor (MSPI), a 32- to 33-kDa Kunitz-type serine protease inhibitor, inhibits plasmin and trypsin. Because plasmin and trypsin are involved in the activation of promatrix metalloproteases proMMP-1 and proMMP-3, we investigated the role of TFPI-2/MSPI in the activation of these proenzymes. Both plasmin and trypsin activated proMMP-1 by converting the 53-kDa proenzyme to the partially active 43-kDa polypeptide; this activity was inhibited by TFPI-2/MSPI. Similarly, TFPI-2/MSPI inhibited the conversion of 66-kDa proMMP-3 to the activated 45- and 30-kDa polypeptides by plasmin and trypsin. Because plasmin is involved in the physiological activation of proMMP-3, we tested whether TFPI-2/MSPI inhibits the activation of proMMP-3 by HT-1080 fibrosarcoma cells and urokinase-charged HeLa cells. We found that the inhibitor inhibited proMMP-3 activation by HT-1080 cells and urokinase-charged HeLa cells. Collectively, our results suggest that TFPI-2/MSPI indirectly regulates MMP-1- and MMP-3-catalyzed matrix proteolysis by regulating the activation of proMMP-1 and proMMP-3.
 ...
PMID:Regulation of ProMMP-1 and ProMMP-3 activation by tissue factor pathway inhibitor-2/matrix-associated serine protease inhibitor. 1008 61

Glioblastoma is the most malignant primary brain tumor. Due to its highly promigratory and proinvasive properties, standard therapy including surgery, chemotherapy and radiation fails in eradicating this highly aggressive type of cancer. Here, we evaluated the role of TFPI-2, a Kunitz-type serine protease inhibitor, which has been previously described as a tumor suppressor gene in several types of cancer, including glioma. TFPI-2 expression was absent in five of nine investigated high-grade glioma cell lines. Lentiviral knockdown of TFPI-2 in two of the TFPI-2-expressing cell lines (MZ-18 and Hs 638) was associated with pronounced changes in the cellular behavior: glioma cell proliferation, migration and invasion were significantly increased in TFPI-2 knockdown cells in comparison to empty vector-transfected control cells. Since TFPI-2 might exert its tumor suppressor function by inhibiting MMPs, we subsequently analyzed the effects of specific MMP inhibitors on cell invasion of TFPI-2 KD cells vs. control cells. The data obtained from these experiments suggest that the anti-invasive properties of TFPI-2 are associated with inhibition of MMP-1 and MMP-2, while inhibition of MMP-9 seems to play a minor role in this context. Our findings underscore the important role of TFPI-2 as a tumor suppressor gene and indicate that TFPI-2 may be a useful diagnostic marker for the aggressive phenotype of glial tumors.
 ...
PMID:Knockdown of TFPI-2 promotes migration and invasion of glioma cells. 2153 Jun 12