Shanghai Institute of Immunology, Department of Immunology and Microbiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Pancreatic Surgery, Pancreatic Cancer Institute, Fudan University, Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Shanghai, China.
J Cell Mol Med. 2021 Jun;25(12):5443-5456. doi: 10.1111/jcmm.16555. Epub 2021 May 6.
Neutrophil extracellular DNA traps (NETs) are newly discovered forms of activated neutrophils. Increasing researches have shown that NETs play important roles in cancer progression. Our previous study has proved that tumour-infiltrating NETs could predict postsurgical survival in patients with pancreatic ductal adenocarcinoma (PDAC). However, the roles of NETs on the progression of pancreatic cancer are unknown. Here, we investigated the effects of NETs on pancreatic cancer cells. Results showed that both PDAC patients' and normal individuals' neutrophils-derived NETs could promote migration and invasion of pancreatic cancer cells with epithelial-mesenchymal transition. Further, study confirmed that EGFR/ERK pathway played an important role in this progression. The addition of neutralizing antibodies for IL-1β could effectively block the activation of EGFR/ERK companied with reduction of EMT, migration and invasion. Taken together, NETs facilitated EMT, migration and invasion via IL-1β/EGFR/ERK pathway in pancreatic cancer cells. Our study suggests that NETs may provide promising therapeutic targets for pancreatic cancer.
中性粒细胞胞外诱捕网（NETs）是新近发现的激活中性粒细胞的形式。越来越多的研究表明，NETs 在癌症进展中发挥着重要作用。我们之前的研究已经证明，肿瘤浸润 NETs 可以预测胰腺导管腺癌（PDAC）患者的术后生存。然而，NETs 在胰腺癌进展中的作用尚不清楚。在这里，我们研究了 NETs 对胰腺癌细胞的影响。结果表明，PDAC 患者和正常人的中性粒细胞衍生的 NETs 均可促进具有上皮-间充质转化的胰腺癌细胞的迁移和侵袭。进一步的研究证实，EGFR/ERK 通路在此过程中起着重要作用。添加中和抗体可有效阻断 IL-1β 激活伴随 EMT、迁移和侵袭减少。总之，NETs 通过 IL-1β/EGFR/ERK 通路促进胰腺癌细胞的 EMT、迁移和侵袭。我们的研究表明，NETs 可能为胰腺癌提供有前途的治疗靶点。
