Takano Kenichi, Kondo Atsushi, Kurose Makoto, Yamashita Keiji, Nomura Kazuaki, Obata Kazufumi, Murayama Kosuke, Ito Fumie, Himi Tetsuo
Adv Otorhinolaryngol. 2016;77:98-104. doi: 10.1159/000441884. Epub 2016 Apr 26.
Inflammasomes, large protein complexes typically consisting of a Nod-like receptor (NLR), adapter protein apoptosis-associated speck-like protein containing CARD (ASC) and caspase-1, are postulated to be activated in response to danger signals arising from tumors. Inflammasomes are thought to have critical but contrasting roles through facilitating antitumor immunity and inducing oncogenic factors. However, the role and function of inflammasomes in oropharyngeal carcinoma remain unclear. We analyzed nine specimens of oropharyngeal squamous cell carcinoma (SCC) and determined the expression of NLRP3, ASC, interleukin (IL)-1β, IL-18 and caspase-1 in the specimens with and without human papilloma virus (HPV) infection using immunohistochemistry, and analyzed the correlations between the altered expression of these proteins and clinicopathological factors of oropharyngeal SCC. We found strong expression of NLRP3, ASC, IL-1β, IL-18 and caspase-1 in human oropharyngeal SCC and weak or no expression of these proteins in normal tonsils. Furthermore, the distribution of mindbomb E3 ubiquitin protein ligase 1 and inflammasome-associated proteins in oropharyngeal SCC was not significantly different; there was no correlation between the expression of inflammasome-associated proteins and HPV infection. These findings suggest that inflammasomes in oropharyngeal SCC play a key role through facilitating antitumor immunity and the possibility of new roles for inflammasomes in the oropharynx.
炎性小体是一种大型蛋白质复合物,通常由核苷酸结合寡聚化结构域样受体(NLR)、含半胱天冬酶激活和招募结构域的凋亡相关斑点样蛋白(ASC)以及半胱天冬酶-1组成,据推测,它会在肿瘤产生的危险信号作用下被激活。炎性小体被认为通过促进抗肿瘤免疫和诱导致癌因子发挥关键但相反的作用。然而,炎性小体在口咽癌中的作用和功能仍不清楚。我们分析了9例口咽鳞状细胞癌(SCC)标本,采用免疫组织化学方法测定了有和无人乳头瘤病毒(HPV)感染标本中NLRP3、ASC、白细胞介素(IL)-1β、IL-18和半胱天冬酶-1的表达,并分析了这些蛋白表达改变与口咽SCC临床病理因素之间的相关性。我们发现NLRP3、ASC、IL-1β、IL-18和半胱天冬酶-1在人类口咽SCC中表达强烈,而在正常扁桃体中这些蛋白表达较弱或无表达。此外,口咽SCC中mindbomb E3泛素蛋白连接酶1和炎性小体相关蛋白的分布无显著差异;炎性小体相关蛋白的表达与HPV感染之间无相关性。这些发现表明,口咽SCC中的炎性小体通过促进抗肿瘤免疫发挥关键作用,并提示炎性小体在口咽中可能具有新的作用。