Interleukin-33 enhances programmed oncosis of ST2L-positive low-metastatic cells in the tumour microenvironment of lung cancer

Cell Death & Disease
M AkimotoK Takenaga

Abstract

The proinflammatory interleukin-33 (IL-33) binds to its receptor ST2L on the surface of immune cells and stimulates the production of Th2 cytokines; however, the effects of IL-33 on tumour cells are poorly understood. Here we show that ST2 was significantly downregulated in human lung cancer tissues and cells compared with normal lung tissues and cells. IL-33 expression was also inversely correlated with the stages of human lung cancers. In accordance with this finding, low-metastatic cells but not high-metastatic cells derived from Lewis lung carcinoma expressed functional ST2L. IL-33 was abundantly present in the tumours established by the low-metastatic cells compared with those formed by the high-metastatic cells. Although the low-metastatic cells scarcely expressed IL-33 in vitro, these cells did expry 6ess this molecule in vivo, likely due to stimulation by intratumoural IL-1β and IL-33. Importantly, IL-33 enhanced the cell death of ST2L-positive low-metastatic cells, but not of ST2L-negative high-metastatic cells, under glucose-depleted, glutamine-depleted and hypoxic conditions through p38 MAPK and mTOR activation, and in a mitochondria-dependent manner. The cell death was characterised by cytoplasmic blisters and karyo...Continue Reading

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Citations

May 16, 2018·Experimental Biology and Medicine·Pawel SowaMonika Adamczyk-Sowa
Sep 27, 2018·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Jaewoo HongP Charles Lin
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Sep 13, 2018·International Journal of Molecular Sciences·Kristen M LarsenMaria Marjorette O Peña
Jun 17, 2021·European Journal of Immunology·Wenyi JiangYi Zhang

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Datasets Mentioned

BETA
GSE31210

Methods Mentioned

BETA
SMA
flow cytometry
electrophoresis
PCR
ELISA

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