Cancer cells deploy lipocalin-2 to collect limiting iron in leptomeningeal metastasis.
Journal
Science (New York, N.Y.)
ISSN: 1095-9203
Titre abrégé: Science
Pays: United States
ID NLM: 0404511
Informations de publication
Date de publication:
17 07 2020
17 07 2020
Historique:
received:
21
08
2019
accepted:
01
06
2020
entrez:
18
7
2020
pubmed:
18
7
2020
medline:
11
8
2020
Statut:
ppublish
Résumé
The tumor microenvironment plays a critical regulatory role in cancer progression, especially in central nervous system metastases. Cancer cells within the cerebrospinal fluid (CSF)-filled leptomeninges face substantial microenvironmental challenges, including inflammation and sparse micronutrients. To investigate the mechanism by which cancer cells in these leptomeningeal metastases (LM) overcome these constraints, we subjected CSF from five patients with LM to single-cell RNA sequencing. We found that cancer cells, but not macrophages, within the CSF express the iron-binding protein lipocalin-2 (LCN2) and its receptor SCL22A17. These macrophages generate inflammatory cytokines that induce cancer cell LCN2 expression but do not generate LCN2 themselves. In mouse models of LM, cancer cell growth is supported by the LCN2/SLC22A17 system and is inhibited by iron chelation therapy. Thus, cancer cells appear to survive in the CSF by outcompeting macrophages for iron.
Identifiants
pubmed: 32675368
pii: 369/6501/276
doi: 10.1126/science.aaz2193
pmc: PMC7816199
mid: NIHMS1652359
doi:
Substances chimiques
LCN2 protein, human
0
Lipocalin-2
0
Iron
E1UOL152H7
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
276-282Subventions
Organisme : NCI NIH HHS
ID : U2C CA233284
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA245499
Pays : United States
Organisme : NCI NIH HHS
ID : L30 CA189044
Pays : United States
Organisme : NCI NIH HHS
ID : R35 CA220508
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Commentaires et corrections
Type : CommentIn
Type : CommentIn
Informations de copyright
Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.
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