IL-10 derived from M2 macrophage promotes cancer stemness via JAK1/STAT1/NF-κB/Notch1 pathway in non-small cell lung cancer

Li Yang, Ying Dong, Yanjun Li, Dong Wang, Shasha Liu, Dan Wang, Qun Gao, Shaofei Ji, Xinfeng Chen, Qingyang Lei, Wenyi Jiang, Liping Wang, Bin Zhang, Jane J. Yu, Yi Zhang*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

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-κB/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.

Original languageEnglish (US)
Pages (from-to)1099-1110
Number of pages12
JournalInternational Journal of Cancer
Volume145
Issue number4
DOIs
StatePublished - Aug 15 2019

Keywords

  • IL-10
  • cancer stem cells
  • non-small cell lung cancer
  • tumor microenvironment
  • tumor-associated macrophages

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'IL-10 derived from M2 macrophage promotes cancer stemness via JAK1/STAT1/NF-κB/Notch1 pathway in non-small cell lung cancer'. Together they form a unique fingerprint.

Cite this