A role for aberrantly expressed nuclear localized decorin in migration and invasion of dysplastic and malignant oral epithelial cellsReport as inadecuate




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Head and Neck Oncology

, 3:44

First Online: 29 September 2011Received: 19 September 2011Accepted: 29 September 2011

Abstract

BackgroundOral cancer is the sixth most common malignancy worldwide with a mortality rate that is higher than many other cancers. Death usually occurs as a result of local invasion and regional lymph node metastases. Decorin is a multifunctional proteoglycan of the extracellular matrix that affects the biology of various types of cancer. Previously; we have shown that decorin is aberrantly expressed in the nucleus in human dysplastic oral keratinocytes DOK and malignant squamous cells carcinoma SCC-25 and human biopsy tissues. In this study, we examined the role of nuclear decorin in oral cancer progression.

Materials and methodsWe have used a post-transcriptional gene silencing RNA interference approach to stably knockdown nuclear decorin gene expression in DOK and SCC-25 cells using a specific shRNA plasmid and a combination of immunological and molecular techniques to study nuclear decorin function in these oral epithelial cell lines.

ResultsMore than 80% decorin silencing-knockdown was achieved as confirmed by real time PCR and western blot analysis in both DOK and SCC-25 cells. This RNA interference-mediated knockdown of nuclear decorin expression resulted in significantly reduced invasion and migration in these cell lines as measured by Matrigel™ coated and uncoated Trans well chamber assays respectively. Decorin silencing also resulted in reduced IL-8 mRNA and proteins levels in these cell lines. Culturing decorin silenced DOK and SCC-25 cells, with recombinant human IL-8 or IL-8 containing conditioned medium from respective un-transfected cells for 24 h prior to migration and invasion experiments, resulted in the salvation of reduced migration and invasion phenotype. Furthermore, we found that nuclear localized decorin interacts with EGFR in the nuclear fractions of both DOK and SCC-25 cells. Interestingly, EGFR trans activation has previously been shown to be involved in IL-8 production in various epithelia.

ConclusionsTaken together, our results indicate that nuclear localized decorin plays an important role in migration and invasion of oral cancer cells and thus may present as a novel potential target for the treatment of oral cancer.

KeywordsOral Cancer decorin functional genomics shRNA invasion migration IL-8 EGFR Electronic supplementary materialThe online version of this article doi:10.1186-1758-3284-3-44 contains supplementary material, which is available to authorized users.

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Author: Nyla Dil - Abhijit G Banerjee

Source: https://link.springer.com/







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