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Matrix metalloproteinase-13 is regulated by toll-like receptor-9 in colorectal cancer cells and mediates cellular migration.
MedLine Citation:
PMID:  22866107     Owner:  NLM     Status:  Publisher    
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.
Timo Rath; Julia Stöckle; Martin Roderfeld; Annette Tschuschner; Jürgen Graf; Elke Roeb
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-3-21
Journal Detail:
Title:  Oncology letters     Volume:  2     ISSN:  1792-1082     ISO Abbreviation:  Oncol Lett     Publication Date:  2011 May 
Date Detail:
Created Date:  2012-8-6     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101531236     Medline TA:  Oncol Lett     Country:  -    
Other Details:
Languages:  ENG     Pagination:  483-488     Citation Subset:  -    
Department of Gastroenterology, Medical Clinic II, Justus-Liebig-University, Giessen.
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