Abstract
BackgroundInflammasomes are reported to be abnormally expressed and activated in several malignancies and play important roles in tumor development. The present study was designed to investigate the expression and function of the NLR family pyrin domain containing protein 3 (NLRP3) inflammasome in oral squamous cell carcinoma (OSCC).MethodsNLRP3 expression in OSCC cell lines and the normal human immortalized oral epithelial cells (HIOEC) was determined by real-time PCR and western blot. Immunohistochemistry was used to examine the expression of NLRP3 and IL-1β in the paraffin-embedded OSCC tissues. The proliferation of OSCC cells was detected by the 3-(4,5-dimethylthiazol- 2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and cell colony formation ability of the OSCC cells was also evaluated. Tumor cell migration or invasion was measured by the transwell assay and related protein markers were determined by western blot. A mouse xenograft model was established to investigate the OSCC tumor growth in vivo.ResultsSignificant higher expression of NLRP3 was observed in the OSCC cells. Obvious expression of NLRP3 and IL-1β was found in the paraffin-embedded OSCC tissues, and the NLRP3 expression levels were correlated with the tumor size, lymphonode metastatic status and IL-1β expression. Downregulating NLRP3 expression markedly reduced the cleavage of caspase-1 and production of IL-1β in OSCC cells. NLRP3 knockdown also inhibited the proliferation, migration and invasion of OSCC cells. Further investigation indicated that expressions of E-cadherin and vimentin in OSCC cells were increased, while N-cadherin expression was decreased after NLRP3 knockdown. Downregulating NLRP3 expression in OSCC cells significantly reduced the tumor growth in vivo.ConclusionsOur data suggested that the increased expression of NLRP3 in OSCC was associated with tumor growth and metastasis. NLRP3 may be considered as a potential target for OSCC therapy.
Highlights
Inflammasomes are reported to be abnormally expressed and activated in several malignancies and play important roles in tumor development
NLR family pyrin domain containing protein 3 (NLRP3) expression is increased in oral squamous cell carcinoma (OSCC) cells To determine the expression levels of NLRP3 in OSCC cells, RT-PCR and western blot analysis were performed
NLRP3 expression is associated with the clinicopathological characteristics of OSCC patients To further identify the expression of NLRP3 in tissues, IHC staining was performed in 77 OSCC specimens
Summary
Inflammasomes are reported to be abnormally expressed and activated in several malignancies and play important roles in tumor development. The present study was designed to investigate the expression and function of the NLR family pyrin domain containing protein 3 (NLRP3) inflammasome in oral squamous cell carcinoma (OSCC). Studies of Fujita et al reported that the constitutively active NLR pyrin domain-containing protein 3 (NLRP3) inflammasome in human melanoma cells mediated autoinflammation via caspase-1 processing and IL-1β secretion [16] and NLRP1 inflammasome activation promoted tumor growth in metastatic melanoma [17]. Kolb et al indicated obesity associated NLR family CARD domain-containing protein 4 (NLRC4) inflammasome activation drove breast cancer progression [19]. The roles of inflammasomes, NLRP3 inflammasome in OSCC have not been fully elucidated
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