1. Academic Validation
  2. Neutrophil extracellular traps induce tumor metastasis through dual effects on cancer and endothelial cells

Neutrophil extracellular traps induce tumor metastasis through dual effects on cancer and endothelial cells

  • Oncoimmunology. 2022 Mar 16;11(1):2052418. doi: 10.1080/2162402X.2022.2052418.
Ze-Zhou Jiang 1 2 Zhi-Peng Peng 1 Xing-Chen Liu 1 Hao-Fan Guo 1 Meng-Meng Zhou 1 Da Jiang 1 Wan-Ru Ning 1 Yu-Fan Huang 1 Limin Zheng 1 2 Yan Wu 1
Affiliations

Affiliations

  • 1 Guangdong Province Key Laboratory of Pharmaceutical Functional Genes, Moe Key Laboratory of Gene Function and Regulation, School of Life Sciences, Sun Yat-sen University, Guangzhou, P. R. China.
  • 2 State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, P. R. China.
Abstract

Neutrophils constitute a major component in human hepatocellular carcinoma (HCC) and can facilitate disease progression via poorly understood mechanisms. Here, we show that neutrophil extracellular traps (NETs) formation was increased in human HCC tumor tissues than in paired non-tumor liver tissues. Mechanism study revealed that tumor-induced metabolic switch toward glycolysis and pentose phosphate pathway in tumor infiltrating neutrophils promoted NETs formation in a Reactive Oxygen Species dependent-manner. NETs subsequently induced the migration of Cancer cells and down-regulation of tight junction molecules on adjacent endothelial cells, thus facilitating tumor intravasation and metastasis. Accordingly, NETs depletion could inhibit tumor metastasis in mice in vivo, and the infiltration levels of NETs-releasing neutrophils were negatively associated with patient survival and positively correlated with tumor metastasis potential of HCC patients. Our results unveiled a pro-metastatic role of NETs in the milieu of human HCC, and pointed to the importance of metabolic reprogramming in shaping their characteristics, thus providing an applicable efficient target for anti-cancer therapies.

Keywords

Neutrophils; hepatocellular carcinoma; metabolic switch; neutrophil-extracellular traps; tumor metastasis.

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