Coculture with macrophages alters ferroptosis susceptibility of triple-negative cancer cells

Konishi, Hiroto; Haga, Yuya; Okumura, Moe; Tsujino, Hirofumi; Higashisaka, Kazuma; Tsutsumi, Yasuo

doi:https://doi.org/10.1038/s41420-024-01884-w

Coculture with macrophages alters ferroptosis susceptibility of triple-negative cancer cells

Konishi, Hiroto; Haga, Yuya; Okumura, Moe et al.

Cell Death Discovery, 2024, 10(1), 108

アクセス数:716件（2025-07-12 15:02 集計）

固定URL: https://hdl.handle.net/11094/97799

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タイトル	Coculture with macrophages alters ferroptosis susceptibility of triple-negative cancer cells
著者	著者名 Konishi, Hiroto
	NRID 1000030888863 1000030888863 ORCID 0000-0003-4148-2256 0000-0003-4148-2256 researchmap permalink 30888863 30888863 Scopus Author ID 57211023415 57211023415 著者名 Haga, Yuya
	著者名 Okumura, Moe
	NRID 1000010707144 1000010707144 researchmap permalink htsujino htsujino Scopus Author ID 36667726200 36667726200 著者名 Tsujino, Hirofumi
	NRID 1000020646757 1000020646757 researchmap permalink read646757 read646757 Scopus Author ID 35603386200 35603386200 著者名 Higashisaka, Kazuma
	NRID 1000050263306 1000050263306 researchmap permalink ytsutsumi ytsutsumi Scopus Author ID 7202474093 7202474093 著者名 Tsutsumi, Yasuo
内容	Konishi H., Haga Y., Okumura M., et al. Coculture with macrophages alters ferroptosis susceptibility of triple-negative cancer cells. Cell Death Discovery 10, 108 (2024); https://doi.org/10.1038/s41420-024-01884-w.
抄録	Various treatment options, such as molecular targeted drugs and immune checkpoint blockades, are available for patients with cancer. However, some cancer types are refractory to molecular targeted therapies or acquire drug resistance after long-term treatment. Thus, ferroptosis, a newly defined type of programmed cell death caused by the iron-dependent accumulation of lipid peroxidation, has gained attention as a novel cancer treatment strategy. Understanding cell–cell interactions in the tumor microenvironment is important for the clinical application of ferroptosis inducers. However, the effects of cell–cell interactions on ferroptosis sensitivity remain unclear. Thus, we aimed to evaluate the effects of macrophage–cancer cell interactions on ferroptosis induction. Coculture experiments showed that conditioned medium prepared from macrophages did not alter the ferroptosis sensitivity of cancer cells. By contrast, coculture via transwell, which enables cell–cell interactions through secretion, increased the sensitivity of cancer cells to ferroptosis inducers. Additionally, direct coculture increased the susceptibility of cancer cells to RSL3-induced ferroptosis. Mechanistically, coculture with macrophages upregulated the levels of intracellular ferrous ions and lipid peroxidation in cancer cells. These findings provide novel insights into the mechanisms by which cell–cell interactions influence ferroptosis induction and application of ferroptosis inducers as a cancer treatment option.
出版者	Springer Nature
収録物名	Cell Death Discovery
巻(号)	10(1)
ページ	108
刊行年月	2024-03-01
言語	英語
ハンドルURL	https://hdl.handle.net/11094/97799
eISSN	20587716
関連情報 (isIdenticalTo)	DOI (出版社版) https://doi.org/10.1038/s41420-024-01884-w
アクセス権	open access
権利情報	This article is licensed under a Creative Commons Attribution 4.0 International License.
出版タイプ	Version of Record
カテゴリ	学術雑誌論文 Journal Article

資源タイプ	学術雑誌論文
ローカル資源タイプ	学術雑誌論文
DCTERMS.bibliographicCitation	Cell Death Discovery. 2024, 10(1), p. 108
DC.title	Coculture with macrophages alters ferroptosis susceptibility of triple-negative cancer cells
DC.creator	Konishi, Hiroto
	Haga, Yuya
	Okumura, Moe
	Tsujino, Hirofumi
	Higashisaka, Kazuma
	Tsutsumi, Yasuo
DC.publisher	Springer Nature
DC.language' scheme='DCTERMS.RFC1766	英語
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2024-03-01
DC.identifier	https://doi.org/10.1038/s41420-024-01884-w
DC.description	Konishi H., Haga Y., Okumura M., et al. Coculture with macrophages alters ferroptosis susceptibility of triple-negative cancer cells. Cell Death Discovery 10, 108 (2024); https://doi.org/10.1038/s41420-024-01884-w.
DCTERMS.abstract	Various treatment options, such as molecular targeted drugs and immune checkpoint blockades, are available for patients with cancer. However, some cancer types are refractory to molecular targeted therapies or acquire drug resistance after long-term treatment. Thus, ferroptosis, a newly defined type of programmed cell death caused by the iron-dependent accumulation of lipid peroxidation, has gained attention as a novel cancer treatment strategy. Understanding cell–cell interactions in the tumor microenvironment is important for the clinical application of ferroptosis inducers. However, the effects of cell–cell interactions on ferroptosis sensitivity remain unclear. Thus, we aimed to evaluate the effects of macrophage–cancer cell interactions on ferroptosis induction. Coculture experiments showed that conditioned medium prepared from macrophages did not alter the ferroptosis sensitivity of cancer cells. By contrast, coculture via transwell, which enables cell–cell interactions through secretion, increased the sensitivity of cancer cells to ferroptosis inducers. Additionally, direct coculture increased the susceptibility of cancer cells to RSL3-induced ferroptosis. Mechanistically, coculture with macrophages upregulated the levels of intracellular ferrous ions and lipid peroxidation in cancer cells. These findings provide novel insights into the mechanisms by which cell–cell interactions influence ferroptosis induction and application of ferroptosis inducers as a cancer treatment option.
DC.rights	This article is licensed under a Creative Commons Attribution 4.0 International License.
DC.format	97799
citation_title	Coculture with macrophages alters ferroptosis susceptibility of triple-negative cancer cells
citation_author	Konishi, Hiroto
	Haga, Yuya
	Okumura, Moe
	Tsujino, Hirofumi
	Higashisaka, Kazuma
	Tsutsumi, Yasuo
citation_publisher	Springer Nature
citation_language	英語
citation_date	2024-03-01
citation_journal_title	Cell Death Discovery
citation_volume	10
citation_issue	1
citation_firstpage	108
citation_doi	https://doi.org/10.1038/s41420-024-01884-w
citation_public_url	https://hdl.handle.net/11094/97799

Coculture with macrophages alters ferroptosis susceptibility of triple-negative cancer cells

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