期刊
ONCOLOGY REPORTS
卷 38, 期 5, 页码 2959-2966出版社
SPANDIDOS PUBL LTD
DOI: 10.3892/or.2017.5942
关键词
neutrophils; EMT; metastasis; microenvironment; gastric cancer
类别
资金
- National Natural Science Foundation of China [81672416, 81201660]
- Natural Science Foundation of Jiangsu Province [BK20141303]
- Key Research and Development Project of Zhenjiang [SH2015034]
- Starting Foundation for Senior Talents of Jiangsu University [13JDG086]
- Qing Lan project of Jiangsu Province
- '333' project of Jiangsu Province
- Foundation for Young Academic Leader of Jiangsu University
Emerging evidence has revealed that neutrophils have phenotypic and functional plasticity. Neutrophils could be polarized towards a pro-tumor phenotype by tumor-derived factors. In the present study, we investigated the role of the interaction with neutrophils on the functions of gastric cancer cells in vitro. Human promyelocytic leukemia HL-60 cells were induced to differentiate into neutrophil-like cells (HL-60N) using dimethyl sulfoxide (DMSO). Human gastric cancer cells were co-cultured with HL-60N cells or treated with the conditioned medium (CM) of cancer-activated HL-60N cells. The migration and invasion of gastric cancer cells were significantly enhanced while their proliferation was minimally altered. The expression of pro-inflammatory factors including IL-6, IL-8, IL-1 beta, and TNF alpha was significantly increased in cancer-activated HL-60N cells, which induced the activation of the ERK pathway and epithelial-mesenchymal transition (EMT) in gastric cancer cells. Blocking the ERK pathway activation reversed the promoting effects of cancer-activated HL-60N cells on gastric cancer cell migration and invasion. In addition, mouse gastric cancer cell derived CM could also increase the expression of pro-inflammatory factors in mouse bone marrow neutrophils, which in turn enhanced the migration and invasion of mouse gastric cancer cells. Collectively, our findings revealed that the interaction with neutrophils promoted gastric cancer cell migration and invasion through the activation of the ERK pathway and the induction of EMT, indicating that neutrophils may play an important role in gastric cancer metastasis. Therefore, targeting neutrophil-cancer cell interaction may provide a new strategy for the treatment of gastric cancer.
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