Leukotriene Synthesis Is Critical for Medulloblastoma Progression.
Animals
Arachidonate 5-Lipoxygenase
/ deficiency
Astrocytes
/ metabolism
Carcinogenesis
/ genetics
Cell Line, Tumor
Cell Proliferation
/ genetics
Disease Progression
Gene Expression Regulation, Neoplastic
/ genetics
Hedgehog Proteins
/ genetics
Humans
Leukotrienes
/ biosynthesis
Medulloblastoma
/ genetics
Mice
Mice, Knockout
RNA, Small Interfering
/ genetics
Signal Transduction
/ genetics
Journal
Clinical cancer research : an official journal of the American Association for Cancer Research
ISSN: 1557-3265
Titre abrégé: Clin Cancer Res
Pays: United States
ID NLM: 9502500
Informations de publication
Date de publication:
01 11 2019
01 11 2019
Historique:
received:
02
11
2018
revised:
18
04
2019
accepted:
02
07
2019
pubmed:
14
7
2019
medline:
9
9
2020
entrez:
14
7
2019
Statut:
ppublish
Résumé
Here, we examined the role of leukotrienes, well-known inflammatory mediators, in the tumorigenesis of hedgehog pathway-associated medulloblastoma, and tested the efficacies of antagonists of leukotriene biosynthesis in medulloblastoma treatment. Leukotriene was significantly upregulated in medulloblastoma cells. Increased leukotriene synthesis relied on hedgehog ligand secreted by astrocytes, a major component of medulloblastoma microenvironment. Leukotriene stimulated tumor cells to express Nestin, a cytoskeletal protein essential for medulloblastoma growth. Genetic blockage of leukotriene synthesis dramatically suppressed medulloblastoma cell proliferation and tumor growth Our findings reveal a novel signaling pathway that is critical for medulloblastoma cell proliferation and tumor progression, and that leukotriene biosynthesis represents a promising therapeutic target for medulloblastoma treatment.
Identifiants
pubmed: 31300449
pii: 1078-0432.CCR-18-3549
doi: 10.1158/1078-0432.CCR-18-3549
pmc: PMC6825543
mid: NIHMS1534110
doi:
Substances chimiques
Hedgehog Proteins
0
Leukotrienes
0
RNA, Small Interfering
0
Arachidonate 5-Lipoxygenase
EC 1.13.11.34
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
6475-6486Subventions
Organisme : NCI NIH HHS
ID : R01 CA178380
Pays : United States
Organisme : NCI NIH HHS
ID : R21 CA185504
Pays : United States
Informations de copyright
©2019 American Association for Cancer Research.
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