P2X7 receptor and NLRP3 inflammasome activation in head and neck cancer.
In this study, we investigated purinergic receptor P2X7 and NACHT, LRR and PYD domains-containing protein 3 (NLRP3) inflammasome expressions, and their role in head and neck cancer. We found upregulation of purinergic receptor P2X7 and all NLRP3 inflammasome components in biopsied head and neck squamous cell carcinoma tissues. Similarly, the expression of purinergic receptor P2X7, apoptosis-associated speck-like protein containing CARD, and pro-form caspase 1 in A253 cells derived from epidermoid carcinoma were highly upregulated in comparison to normal Human Salivary Gland cell line. Active caspase-1 and its final product, active interleukin-1β, both increased in primed A253 cells stimulated with purinergic receptor P2X7 agonists, while this elevated NLRP3 inflammasome activity was suppressed by purinergic receptor P2X7 antagonists. However, we observed none of these effects in Human Salivary Gland cells. Inhibition of both NLRP3 inflammasome and purinergic receptor P2X7 led to the significant cell death of primed A253 cells, but had no effect on the viability of primed HSG cells or the primary cultured human fibroblast cells. Furthermore, inhibition of either purinergic receptor P2X7 or NLRP3 inflammasome decreased invasiveness of A253, and this effect became more evident when both purinergic receptor P2X7 and NLRP3 inflammasome were simultaneously blocked. Therefore, it is concluded that the purinergic receptor P2X7 and the activation of NLRP3 inflammasome play important roles in the survival and invasiveness of head and neck squamous cell carcinoma in humans.
['Bae|Ju Young|JY|', 'Lee|Sang-Woo|SW|', 'Shin|Yong-Hwan|YH|', 'Lee|Jong-Ho|JH|', 'Jahng|Jeong Won|JW|', 'Park|Kyungpyo|K|']
D000368:Aged D015415:Biomarkers D045744:Cell Line, Tumor D002470:Cell Survival D005260:Female D015870:Gene Expression D006258:Head and Neck Neoplasms D006801:Humans D058847:Inflammasomes D008297:Male D008875:Middle Aged D000071199:NLR Family, Pyrin Domain-Containing 3 Protein D058911:Purinergic P2X Receptor Agonists D058920:Purinergic P2X Receptor Antagonists D012333:RNA, Messenger D058486:Receptors, Purinergic P2X7
NLRP3 inflammasome purinergic receptor P2X7 head and neck squamous cell carcinoma A253 cells invasiveness