P2X7 receptor and NLRP3 inflammasome activation in head and neck cancer

// Ju Young Bae 1, * , Sang-Woo Lee 1, * , Yong-Hwan Shin 1 , Jong-Ho Lee 2 , Jeong Won Jahng 3 and Kyungpyo Park 1, * 1 Department of Physiology, School of Dentistry, Seoul National University, Seoul 110–749, Korea 2 Oral and Maxillofacial Surgery, School of Dentistry, Seoul National University, Seoul 110–749, Korea 3 Dental Research Institute, Seoul 110–749, Korea * These authors contributed equally to this work Correspondence to: Kyungpyo Park, email: kppark@snu.ac.kr Keywords: purinergic receptor P2X7, NLRP3 inflammasome, head and neck squamous cell carcinoma, A253 cells, invasiveness Received: November 01, 2016      Accepted: March 29, 2017      Published: April 06, 2017 ABSTRACT 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.