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.
Highlights
Cancer stem cells (CSCs) including lung cancer stem cell (CSC) are cells that can reconstitute cancer tissues and which are considered to be responsible for cancer progression, metastasis and therapeutic resistance, and which result in a poor prognosis[1,2]
Lung CSCs are considered to be responsible for the poor prognosis of patients with lung cancer due to therapeutic resistance and the possible development of recurrence or metastasis[1,16,17]
Lung CSCs have been the subject of great interest
Summary
Cancer stem cells (CSCs) including lung CSCs are cells that can reconstitute cancer tissues and which are considered to be responsible for cancer progression, metastasis and therapeutic resistance, and which result in a poor prognosis[1,2]. As CSCs comprise only a small amount of cancer tissues, sampling limitations remain a major obstacle in CSC research. To overcome this obstacle, we generated CSC-like cells from a colon cancer cell line by the ectopic expression of a small set of transcription factors[4]. We established technologies to generate lung CSC-like cells from human lung cancer cell line A549 by introducing OCT3/4, SOX2 and KLF4, and to construct “lung cancer organoids” in vitro that mimicked human lung cancer tissues. Through the use of these technologies and the evaluation of clinical samples, we identified interleukin-6 as a novel potential therapeutic target for lung cancer stem cells
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