Journal
INTERNATIONAL JOURNAL OF CANCER
Volume 145, Issue 4, Pages 1099-1110Publisher
WILEY
DOI: 10.1002/ijc.32151
Keywords
non-small cell lung cancer; tumor microenvironment; cancer stem cells; tumor-associated macrophages; IL-10
Categories
Funding
- Ministry of Public Health [201501004]
- Science and Technology Department of Henan Province [162102410059]
- Research and Development [2016YFC1303501]
- National Natural Science Foundation of China [81602024, 81771781, 81872410]
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Tumor-associated macrophages (TAMs), key immune cells in the tumor microenvironment, are shown to be closely correlated with the progression of non-small cell lung cancer (NSCLC). Cancer stem cells (CSCs) can contribute to NSCLC progression as well. We aimed to clarify whether TAMs promote the progression of NSCLC by mainly affecting the activities of CSCs. We found that TAM-like cells promoted CSC-like properties in NSCLC cells in vitro, which was mediated by TAM-derived IL-10. TAM-derived IL-10 promoted CSC-like properties of NSCLC cells through JAK1/STAT1/NF-kappa B/Notch1 signaling. Blockade of IL-10/JAK1 signaling inhibited TAM-mediated NSCLC tumor growth in vivo, and the TAM-mediated expression of CSC-related and mesenchymal-related genes in NSCLC. Lastly, expression levels of these signaling molecules were significantly correlated with survival of NSCLC patients. Therefore, IL-10/JAK1 signaling might be a potential therapeutic target for NSCLC treatment.
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