Interleukin-6 blockade attenuates lung cancer tissue construction integrated by cancer stem cells

Sci Rep. 2017 Sep 26;7(1):12317. doi: 10.1038/s41598-017-12017-y.

Abstract

In the present study, we successfully generated lung cancer stem cell (CSC)-like cells by introducing a small set of transcription factors into a lung cancer cell line. In addition to properties that are conventionally referred to as CSC properties, the lung induced CSCs exhibited the ability to form lung cancer-like tissues in vitro with vascular cells and mesenchymal stem cells, which showed structures and immunohistological patterns that were similar to human lung cancer tissues. We named them "lung cancer organoids". We found that interleukin-6 (IL-6), which was expressed in the lung induced CSCs, facilitates the formation of lung cancer organoids via the conversion of mesenchymal stem cells into alpha-smooth muscle actin (αSMA)-positive cells. Interestingly, the combination of anti-IL-6 antibody and cisplatin could destroy the lung cancer organoids, while cisplatin alone could not. Furthermore, IL-6 mRNA-positive cancer cells were found in clinical lung cancer samples. These results suggest that IL-6 could be a novel therapeutic target in lung cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Actins / metabolism
  • Aged
  • Animals
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Proliferation / drug effects
  • Cisplatin / pharmacology
  • Cisplatin / therapeutic use
  • Drug Resistance, Neoplasm
  • Female
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Interleukin-6 / antagonists & inhibitors*
  • Interleukin-6 / metabolism
  • Lung / pathology
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / pathology
  • Male
  • Mesenchymal Stem Cells
  • Mice, Nude
  • Middle Aged
  • Neoplastic Stem Cells / drug effects*
  • Neoplastic Stem Cells / pathology
  • Organoids / drug effects
  • Organoids / pathology
  • Signal Transduction / drug effects
  • Treatment Outcome
  • Xenograft Model Antitumor Assays

Substances

  • ACTA2 protein, human
  • Actins
  • IL6 protein, human
  • Interleukin-6
  • Cisplatin