PMID- 35325945 OWN - NLM STAT- MEDLINE DCOM- 20220328 LR - 20220401 IS - 1673-0860 (Print) IS - 1673-0860 (Linking) VI - 57 IP - 3 DP - 2022 Mar 7 TI - [Ferroptosis in laryngeal squamous cell carcinoma and its regulation by M2 macrophage-derived exosomes]. PG - 324-332 LID - 10.3760/cma.j.cn115330-20210621-00361 [doi] AB - Objective: To investigate ferroptosis in laryngeal squamous cell carcinoma (LSCC) and its regulation by M2 macrophage-derived exosomes. Methods: LSCC and adjacent noncancerous tissue samples were collected from 32 patients treated in the Department of Otorhinolaryngology, Head and Neck Surgery of the Second Affiliated Hospital of Harbin between September 2018 and April 2021, including 26 males and 6 females, aged 43-79 years. The expressions of ferroptosis marker glutathione peroxidase 4(GPX4) in LSCC and adjacent noncancerous tissues were detected by immunohistochemistry and reverse transcriptase-polymerase chain reaction(RT-PCR). The correlations between GPX4 expression and clinicopathological factors in LSCC were analyzed. Biological changes of TU212 cells after treated with ferroptosis-induced agent erastin were detected by transmission electron microscope, cell counting kit-8(CCK-8), clone test, reactive oxygen species(ROS), malondialdehyde(MDA), glutathione(GSH), JC-1, RT-PCR and western blot. Exosomes were isolated from the supernatant of M0/M2 macrophages (M0-exos/M2-exos) and co-incubated with erastin-treated TU212 cells to detect the change of ferroptosis in cells of each group. The data were analyzed by SPSS software of version19.0. Results: GPX4 expression in LSCC tissues was significantly higher than that in adjacent noncancerous tissues (2.04+/-0.65 vs. 0.99+/-0.09, F=30.36, P<0.001), and was closely related to T stage and clinical stage (Ⅰ-Ⅱvs.Ⅲ-Ⅳ: 1.75+/-0.39 vs. 2.18+/-0.71, F=2.25, P<0.05; T1-2 vs. T3-4: 1.71+/-0.42 vs. 2.20+/-0.69, F=2.06, P<0.05). In TU212 cells treated with erastin, mitochondrial crest became smaller, membrane density increased, proliferation rate decreased, intracellular ROS level increased, mitochondrial membrane potential depolarized, GSH content decreased, intracellular MDA level increased and expressions of GPX4 mRNA and protein decreased. Change of M0 into M2 macrophages was induced by IL-4 stimulation. When erastin-treated TU212 cells were incubated with M2-exos, cell proliferation was partially restored and GPX4 expression was enhanced, and also with the recoveries of levels of ROS, MDA and GSH (all P<0.05). Conclusions: Ferroptosis is one of the cell death ways of LSCC. M2-exos may inhibit ferroptosis of LSCC cells. FAU - Xu, L C AU - Xu LC AD - Department of Otorhinolaryngology, Head and Neck Surgery, the Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China. FAU - Cao, J AU - Cao J AD - Department of Otorhinolaryngology, Head and Neck Surgery, the Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China. FAU - Li, W J AU - Li WJ AD - Department of Otorhinolaryngology, Head and Neck Surgery, the Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China. FAU - Yang, Z M AU - Yang ZM AD - Department of Otorhinolaryngology, Head and Neck Surgery, the Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China. FAU - Zhao, R AU - Zhao R AD - Department of Otorhinolaryngology, Head and Neck Surgery, the Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China. FAU - Zhang, J R AU - Zhang JR AD - Department of Otorhinolaryngology, Head and Neck Surgery, the Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China. FAU - Guo, Y AU - Guo Y AD - Department of Otorhinolaryngology, Head and Neck Surgery, the Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China. FAU - Ge, J C AU - Ge JC AD - Department of Otorhinolaryngology, Head and Neck Surgery, the Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China. FAU - Li, L AU - Li L AD - Department of Otorhinolaryngology, Head and Neck Surgery, the Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China. FAU - Sun, Y N AU - Sun YN AD - Department of Otorhinolaryngology, Head and Neck Surgery, the Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China. FAU - Liu, M AU - Liu M AD - Department of Otorhinolaryngology, Head and Neck Surgery, the Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China. FAU - Tian, L L AU - Tian LL AD - Department of Otorhinolaryngology, Head and Neck Surgery, the Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China. LA - chi GR - 82072987/National Natural Science Foundation of China/ PT - Journal Article PL - China TA - Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi JT - Zhonghua er bi yan hou tou jing wai ke za zhi = Chinese journal of otorhinolaryngology head and neck surgery JID - 101247574 SB - IM MH - Adult MH - Aged MH - *Exosomes MH - Female MH - *Ferroptosis MH - *Head and Neck Neoplasms MH - Humans MH - Macrophages MH - Male MH - Middle Aged MH - Squamous Cell Carcinoma of Head and Neck EDAT- 2022/03/25 06:00 MHDA- 2022/03/29 06:00 CRDT- 2022/03/24 22:28 PHST- 2022/03/24 22:28 [entrez] PHST- 2022/03/25 06:00 [pubmed] PHST- 2022/03/29 06:00 [medline] AID - 10.3760/cma.j.cn115330-20210621-00361 [doi] PST - ppublish SO - Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2022 Mar 7;57(3):324-332. doi: 10.3760/cma.j.cn115330-20210621-00361.