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Interleukin-33 enhances programmed oncosis of ST2L-positive low-metastatic cells in the tumour microenvironment of lung cancer
http://hdl.handle.net/2241/00138362
http://hdl.handle.net/2241/0013836243123185-1ec3-491e-893d-3dd86c698753
名前 / ファイル | ライセンス | アクション |
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CD&D_2016-7 (3.8 MB)
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Item type | Journal Article(1) | |||||
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公開日 | 2016-04-01 | |||||
タイトル | ||||||
タイトル | Interleukin-33 enhances programmed oncosis of ST2L-positive low-metastatic cells in the tumour microenvironment of lung cancer | |||||
言語 | ||||||
言語 | eng | |||||
資源タイプ | ||||||
資源 | http://purl.org/coar/resource_type/c_6501 | |||||
タイプ | journal article | |||||
著者 |
Akimoto, M
× Akimoto, M× Hayashi, J-I× Nakae, S× Saito, H× Takenaga, K |
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著者別名 |
林, 純一
× 林, 純一 |
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抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | 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 karyolysis, which are unique morphological features of oncosis. Inevitably, the low-metastatic cells, but not of the high-metastatic cells, grew faster in IL-33−/− mice than in wild-type mice. Furthermore, IL-33 selected for the ST2L-positive, oncosis-resistant high-metastatic cells under conditions mimicking the tumour microenvironment. These data suggest that IL-33 enhances lung cancer progression by selecting for more malignant cells in the tumour microenvironment. | |||||
書誌情報 |
Cell Death and Disease 巻 7, 号 1, p. e2057, 発行日 2016-01 |
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ISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 2041-4889 | |||||
PubMed番号 | ||||||
識別子タイプ | PMID | |||||
関連識別子 | 26775708 | |||||
DOI | ||||||
識別子タイプ | DOI | |||||
関連識別子 | 10.1038/cddis.2015.418 | |||||
権利 | ||||||
権利情報 | © 2016 Macmillan Publishers Limited | |||||
権利 | ||||||
権利情報 | Cell Death and Disease is an open-access journal published by Nature Publishing Group. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ | |||||
著者版フラグ | ||||||
値 | publisher | |||||
出版者 | ||||||
出版者 | Nature Publishing Group |