NLRP3 inflammasome activation promotes inflammation-induced carcinogenesis in head and neck squamous cell carcinoma

• Published in: Journal of experimental & clinical cancer research 2017-09, Vol.36 (1), p.116-13, Article 116
• Main Authors: Huang, Cong-Fa, Chen, Lei, Li, Yi-Cun, Wu, Lei, Yu, Guang-Tao, Zhang, Wen-Feng, Sun, Zhi-Jun
• Format: Article
• Language: English
• Subjects: Analysis; Animals; Cancer stem cells; Carcinogenesis; Carcinogenesis - genetics; Carcinoma, Squamous Cell - genetics; Carcinoma, Squamous Cell - pathology; Complications and side effects; Development and progression; Gene Expression Regulation, Neoplastic - genetics; Genetic aspects; Head and neck cancer; Head and Neck Neoplasms - genetics; Head and Neck Neoplasms - pathology; Humans; Inflammasome; Inflammasomes - antagonists & inhibitors; Inflammasomes - genetics; Inflammation; Inflammation - drug therapy; Inflammation - genetics; Inflammation - pathology; Mice; Mice, Transgenic; Neoplasm Proteins - genetics; Neoplastic Stem Cells - pathology; NLR Family, Pyrin Domain-Containing 3 Protein - antagonists & inhibitors; NLR Family, Pyrin Domain-Containing 3 Protein - genetics; NLRP3; Protein-Serine-Threonine Kinases - genetics; PTEN Phosphohydrolase - genetics; Receptor, Transforming Growth Factor-beta Type I; Receptors, Transforming Growth Factor beta - genetics; Risk factors; SCCHN; Squamous cell carcinoma; Squamous Cell Carcinoma of Head and Neck; Tissue Array Analysis
• ISSN: 1756-9966; 0392-9078; 1756-9966
• DOI: 10.1186/s13046-017-0589-y

NLRP3 inflammasome acts as a danger signal sensor that triggers and coordinates the inflammatory response. However, the roles of NLRP3 inflammasome in the tumorigenesis and development of cancer stem cells (CSCs) of squamous cell carcinoma of the head and neck (SCCHN) remain ambiguous. In our study, tissue microarrays, ELISA, sphere-forming assay, colony formation assay and Western blot analysis were performed to evaluate the effect of NLRP3 inflammasome on the development of CSCs in human SCCHN tissue specimen, cell lines, and transgenic mouse SCCHN model. The components of NLRP3 inflammasome, namely, NLRP3, ASC, Caspase-1, and IL-18 were correlated with CSCs markers BMI1, ALDH1 and CD44 in human SCCHN specimens. Moreover, NLRP3, Caspase-1, IL-1β, and IL-18 were highly expressed in SCCHN cell lines. NLRP3 inflammasome activated by LPS and ATP promoted sphere-forming and colony formation capacities along with an upregulation of BMI1, ALDH1 and CD44. In addition, NLRP3 inflammasome blockade by NLRP3 inhibitor MCC950 reduced sphere and colony number, also decreased the expression of BMI1, ALDH1 and CD44 in SCCHN cell lines. Expression of NLRP3, ASC, Caspase-1, IL-1β, IL-18, BMI1, ALDH1 and CD44 was upregulated in Tgfbr1/Pten 2cKO mouse SCCHN model, and NLRP3 inflammasome expression was closely related to those CSCs makers in mice SCCHN. However, MCC950 treatment reduced the expression of NLRP3 inflammasome, CSCs markers BMI1, ALDH1 and CD44 in Tgfbr1/Pten 2cKO mice SCCHN. In addition, blockade of NLRP3 inflammasome can also delayed the tumor-burdened speed in SCCHN mice. Our study demonstrates that NLRP3 inflammasome was upregulated and associated with the carcinogenesis and CSCs self-renewal activation in SCCHN. NLRP3 inflammasome can be a potential target in the development of novel approaches for head and neck squamous cell carcinoma therapy.