Department of Oral and Maxillofacial Surgery, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China.
Cell Death Dis. 2020 May 22;11(5):391. doi: 10.1038/s41419-020-2538-5.
Necroptosis is a recently discovered form of programmed cell death (PCD) having necrotic-like morphology. However, its presence and potential impact with respect to head and neck squamous cell carcinoma (HNSCC) are still unknown. The aim of this study was to reveal the necroptosis status and its clinicopathological relevance in HNSCC and to establish an in vitro model. We first analyzed the level of p-MLKL, MLKL, and tumor necrosis in HNSCC patient tissues as well as their correlation with clinicopathological features. Results showed that approximately half of the tumor necrosis can be attributed to necroptosis, and the extent of necroptosis is an independent prognostic marker for patient's overall survival and progression-free survival. Then we established and thoroughly verified an in vitro model of necroptosis in two HNSCC cell lines using combined treatment of TNF-α, Smac mimetic and zVAD-fmk (TSZ). At last, we adopted this model and demonstrated that necroptosis can promote migration and invasion of HNSCC cells by releasing damage-associated molecular patterns. In conclusion, our study unveiled the necroptotic status in HNSCC for the first time and provided a novel in vitro model of necroptosis in two HNSCC cell lines. In addition, our results indicated that necroptosis may be a potential cancer promoter in HNSCC. This study may serve as the foundation for future researches of necroptosis in HNSCC.
细胞程序性坏死（Necroptosis）是一种新近发现的具有类似坏死形态的细胞程序性死亡（PCD）形式。然而，其在头颈部鳞状细胞癌（HNSCC）中的存在及其潜在影响尚不清楚。本研究旨在揭示 HNSCC 中细胞程序性坏死的状态及其与临床病理特征的相关性，并建立体外模型。我们首先分析了 HNSCC 患者组织中 p-MLKL、MLKL 和肿瘤坏死因子的水平，并分析了它们与临床病理特征的相关性。结果表明，约一半的肿瘤坏死归因于细胞程序性坏死，细胞程序性坏死的程度是患者总生存和无进展生存的独立预后标志物。然后，我们使用 TNF-α、Smac 模拟物和 zVAD-fmk（TSZ）联合治疗，在两种 HNSCC 细胞系中建立并彻底验证了细胞程序性坏死的体外模型。最后，我们采用该模型证明细胞程序性坏死可以通过释放损伤相关分子模式促进 HNSCC 细胞的迁移和侵袭。总之，本研究首次揭示了 HNSCC 中的细胞程序性坏死状态，并为两种 HNSCC 细胞系中的细胞程序性坏死建立了新的体外模型。此外，我们的结果表明细胞程序性坏死可能是 HNSCC 中的一个潜在的癌症促进因素。本研究可为进一步研究 HNSCC 中的细胞程序性坏死奠定基础。
