Journal article

Publication year: 2011

Pages: 483-488

Journal: Oncology Letters

Volume number: 2

Issue number: 3

ISSN: 1792-1074

eISSN: 1792-1082

Open access status: Gold

DOI Link: https://doi.org/10.3892/ol.2011.276

Publisher: Spandidos Publications

Abstract: 
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 lee 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 mu M 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.

Harvard Citation style: Rath, T., Stoeckle, J., Roderfeld, M., Tschuschner, A., Graf, J. and Roeb, E. (2011) Matrix metalloproteinase-13 is regulated by toll-like receptor-9 in colorectal cancer cells and mediates cellular migration, Oncology Letters, 2(3), pp. 483-488. https://doi.org/10.3892/ol.2011.276

APA Citation style: Rath, T., Stoeckle, J., Roderfeld, M., Tschuschner, A., Graf, J., & Roeb, E. (2011). Matrix metalloproteinase-13 is regulated by toll-like receptor-9 in colorectal cancer cells and mediates cellular migration. Oncology Letters. 2(3), 483-488. https://doi.org/10.3892/ol.2011.276