Inflammatory Activation of Astrocytes Facilitates Melanoma Brain Tropism via the CXCL10-CXCR3 Signaling Axis.
CXCL10
CXCR3
astrocytes
brain metastasis
brain tropism
melanoma
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
13 08 2019
13 08 2019
Historique:
received:
07
01
2019
revised:
20
06
2019
accepted:
11
07
2019
entrez:
15
8
2019
pubmed:
15
8
2019
medline:
5
9
2020
Statut:
ppublish
Résumé
Melanoma is the deadliest skin cancer due to its high rate of metastasis, frequently to the brain. Brain metastases are incurable; therefore, understanding melanoma brain metastasis is of great clinical importance. We used a mouse model of spontaneous melanoma brain metastasis to study the interactions of melanomas with the brain microenvironment. We find that CXCL10 is upregulated in metastasis-associated astrocytes in mice and humans and is functionally important for the chemoattraction of melanoma cells. Moreover, CXCR3, the receptor for CXCL10, is upregulated in brain-tropic melanoma cells. Targeting melanoma expression of CXCR3 by nanoparticle-mediated siRNA delivery or by shRNA transduction inhibits melanoma cell migration and attenuates brain metastasis in vivo. These findings suggest that the instigation of pro-inflammatory signaling in astrocytes is hijacked by brain-metastasizing tumor cells to promote their metastatic capacity and that the CXCL10-CXCR3 axis may be a potential therapeutic target for the prevention of melanoma brain metastasis.
Identifiants
pubmed: 31412247
pii: S2211-1247(19)30930-1
doi: 10.1016/j.celrep.2019.07.033
pii:
doi:
Substances chimiques
CXCL10 protein, human
0
CXCR3 protein, human
0
Chemokine CXCL10
0
Receptors, CXCR3
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1785-1798.e6Informations de copyright
Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.