Garley Marzena, Dziemiańczyk-Pakieła Dorota, Grubczak Kamil, Surażyński Arkadiusz, Dąbrowska Dorota, Ratajczak-Wrona Wioletta, Sawicka-Powierza Jolanta, Borys Jan, Moniuszko Marcin, Pałka Jerzy A, Jabłońska Ewa
Department of Immunology, Medical University of Bialystok, J. Waszyngtona 15A, 15-269 Białystok, Poland.
Department of Maxillofacial and Plastic Surgery, Medical University of Bialystok, M. Skłodowskiej-Curie 24A, 15-276 Białystok, Poland.
J Cancer. 2018 Apr 30;9(11):1958-1965. doi: 10.7150/jca.24238. eCollection 2018.
Taking into account the previously reported relationship between inflammation and carcinogenesis, and the scant amount of data concerning the role of neutrophil extracellular traps (NETs) in carcinogenesis, we decided to study the process of extracellular trap formation in patients with inflammation as well as in patients with cancer occurring in the same location. For preliminary isolation of neutrophils (PMNs), we used Polymorphprep™, then sorted with Microbeads. The cells were recorded in the incubation chamber with a BD Pathway 855 microscope system. Flow cytometric data (MPO+ neutrophils) were acquired on FACSCalibur flow cytometer. Amounts of cfDNA were determined by Abcam's Circulating DNA Quantification Kit. Neutrophils of patients with inflammation and of subjects with stage I/II oral squamous cell carcinoma (OSCC) produce increased amounts of NETs, while stage III/IV OSCC were comparable with the control group. In all of the studied groups of cells stimulation with LPS and rhIL-17 produced more NETs in relation to unstimulated cells. Neutrophil supernatant of inflammation patients and stage I/II cancer patients demonstrated the increased level of cfDNA, which decreased at stage III/IV. Patients with oral inflammations showed an increased rate of MPO+ neutrophils, which was lower than in stage I/II cancer patients and not significantly different than in Stage III/IV cancer patients and the control group. The direction of changes in NETs formation seems to be a new common element shared by inflammation and early stage cancer. Changes in the formation of NETs observed in patients with advanced cancer, other than an early phase or inflammation, indicate an alternative range of NETs involvement depending on different phases of this disease.
考虑到先前报道的炎症与致癌作用之间的关系,以及关于中性粒细胞胞外陷阱(NETs)在致癌作用中作用的数据稀少,我们决定研究炎症患者以及同一部位发生癌症的患者中胞外陷阱形成的过程。为了初步分离中性粒细胞(PMNs),我们使用了Polymorphprep™,然后用微珠进行分选。细胞在BD Pathway 855显微镜系统的孵育室中记录。流式细胞术数据(MPO +中性粒细胞)在FACSCalibur流式细胞仪上获取。cfDNA的量通过Abcam的循环DNA定量试剂盒测定。炎症患者和I/II期口腔鳞状细胞癌(OSCC)患者的中性粒细胞产生的NETs量增加,而III/IV期OSCC与对照组相当。在所有研究的细胞组中,与未刺激的细胞相比,用LPS和rhIL-17刺激产生了更多的NETs。炎症患者和I/II期癌症患者的中性粒细胞上清液显示cfDNA水平升高,在III/IV期降低。口腔炎症患者的MPO +中性粒细胞比例增加,低于I/II期癌症患者,与III/IV期癌症患者和对照组无显著差异。NETs形成的变化方向似乎是炎症和早期癌症共有的一个新的共同因素。在晚期癌症患者中观察到的NETs形成变化,不同于早期或炎症阶段,表明根据该疾病的不同阶段,NETs参与的范围不同。