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

Number of Access:725（2025-07-23 01:06 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/97799

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Title	Coculture with macrophages alters ferroptosis susceptibility of triple-negative cancer cells
Creator	CreatorName Konishi, Hiroto
	NRID 1000030888863 1000030888863 ORCID 0000-0003-4148-2256 0000-0003-4148-2256 researchmap permalink 30888863 30888863 Scopus Author ID 57211023415 57211023415 CreatorName Haga, Yuya
	CreatorName Okumura, Moe
	NRID 1000010707144 1000010707144 researchmap permalink htsujino htsujino Scopus Author ID 36667726200 36667726200 CreatorName Tsujino, Hirofumi
	NRID 1000020646757 1000020646757 researchmap permalink read646757 read646757 Scopus Author ID 35603386200 35603386200 CreatorName Higashisaka, Kazuma
	NRID 1000050263306 1000050263306 researchmap permalink ytsutsumi ytsutsumi Scopus Author ID 7202474093 7202474093 CreatorName Tsutsumi, Yasuo
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.
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.
Publisher	Springer Nature
Source Title	Cell Death Discovery
Volume (Issue)	10(1)
Page	108
Date of Issued	2024-03-01
Language	English
Handle URL	https://hdl.handle.net/11094/97799
eISSN	20587716
Relation.isIdenticalTo	DOI (Publisher Version) https://doi.org/10.1038/s41420-024-01884-w
Access Rights	open access
CopyRight	This article is licensed under a Creative Commons Attribution 4.0 International License.
oaire:version	Version of Record
Category	学術雑誌論文 Journal Article

Resource Type	journal article
Local Type	Journal Article
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	English
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	English
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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