NLRP3-inflammasome activation is associated with epithelial-mesenchymal transition and progression of colorectal cancer.

Abstract

Objective(s):Since activation of NLRP3 inflammasome results in the production of interleukin-1β (IL 1β) and initiation of inflammation as the key players in development of cancer, this study investigated possible activation of NLRP3 inflammasome during the progression of colorectal cancer (CRC) and evaluated the role of NLRP3 inflammasome in epithelial-mesenchymal transition (EMT) process. Materials and Methods:Tissue samples were collected from cancerous (test) and adjacent normal tissues (control) of forty-three male CRC patients (18 grade I and 25 grade III). The gene expression and protein levels were determined by qRT PCR and Western blotting, respectively, and tissue morphological was examined by histopathology. Results:The gene and protein expression levels of transforming growth factor-β (TGF β), IL 1β, nuclear factor κB (NF κB), NLRP3, and caspase-1, as well as the enzyme activity of caspase-1, were significantly increased in CRC. mRNA and protein levels of TGF-β, mature IL 1β, NF κB, and NLRP3 were higher in patients with grade III. EMT markers N cadherin, vimentin, and MMP 9 markedly increased in CRC, and were higher in grade III than grade I, whereas expression of E-cadherin declined by the progression of CRC. NLRP3 protein level was inversely correlated with E-cadherin whereas it positively was correlated with IL 1β, active NF κB, N cadherin, vimentin, and MMP 9. Conclusion:This study for the first time showed that activation of NLRP3 inflammasome contributed to the progression of CRC and is correlated with the EMT process. Although the present study showed that EMT markers are positively correlated with tumor grade, further investigations are required to strongly link the EMT markers to the progression of CRC.