| Matrix metalloproteinase-13 is regulated by toll-like receptor-9 in colorectal cancer cells and mediates cellular migration. | |
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MedLine Citation:
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PMID: 22866107 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Matrix metalloproteinases (MMPs) are associated with cancer cell invasion and metastasis, and are currently the most prominent proteases associated with tumorigenesis. In particular, abundant expression of MMP-13 in colorectal cancer (CRC) is correlated with poor survival and the existence of distant metastasis. As suggested by recent in vitro studies, MMP-13 expression is regulated in a toll-like receptor (TLR)-9-dependent manner. In this study, we quantified the expression of MMP-13, TLR-9 and second messengers of the TLR signal transduction in CRC cells compared to colonic fibroblasts by RT-PCR. Furthermore, the effects of a selective TLR-9 stimulation on the expression of MMP-13 in CRC cells and colonic fibroblasts were analyzed. MMP-13 and TLR-9 as well as associated second messengers were simultaneously up-regulated in LS174 and SW620 cells compared to fibroblasts. Selective TLR-9 agonism with CpG oligonucleotides led to a significant increase in MMP-13 gene expression after 12 h of incubation in LS174 cells and after 12 and 24 h in SW620 cells, but not when using GpC oligonucleotides as a control substance. By contrast, MMP-13 gene expression remained unchanged in colonic fibroblasts following treatment with CpG or GpC oligonucleotides. The effects of selective MMP-13 inhibition on cellular migration were analyzed in Boyden chamber experiments. In the presence of 10 and 20 μM of the specific MMP-13 inhibitor, CL-82198, migration of the LS174 cells was significantly reduced by 55 and 52%, respectively, compared to untreated cells. In conclusion, the results of this study provide evidence of the TLR-9-dependent regulation of MMP-13 in CRC cells, but not in colonic fibroblasts. Since the specific inhibition of MMP-13 significantly reduces the migration of LS174 cells, selective MMP-13 inhibition may be a promising therapeutic strategy in CRC. |
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Authors:
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Timo Rath; Julia Stöckle; Martin Roderfeld; Annette Tschuschner; Jürgen Graf; Elke Roeb |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-3-21 |
Journal Detail:
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Title: Oncology letters Volume: 2 ISSN: 1792-1082 ISO Abbreviation: Oncol Lett Publication Date: 2011 May |
Date Detail:
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Created Date: 2012-8-6 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101531236 Medline TA: Oncol Lett Country: - |
Other Details:
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Languages: ENG Pagination: 483-488 Citation Subset: - |
Affiliation:
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Department of Gastroenterology, Medical Clinic II, Justus-Liebig-University, Giessen. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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