Microphthalmia-Associated Transcription Factor (MITF) Regulates Immune Cell Migration into Melanoma.
Journal
Translational oncology
ISSN: 1936-5233
Titre abrégé: Transl Oncol
Pays: United States
ID NLM: 101472619
Informations de publication
Date de publication:
Feb 2019
Feb 2019
Historique:
received:
29
10
2018
accepted:
31
10
2018
pubmed:
5
12
2018
medline:
5
12
2018
entrez:
4
12
2018
Statut:
ppublish
Résumé
Microphthalmia-associated transcription factor (MITF) is a key transcription factor in melanoma development and progression. MITF amplification and downregulation have been observed in a significant proportion of melanoma patients and correlate with clinical outcomes. Here, we have investigated the effect of MITF on melanoma chemokine expression and immune cell attraction. In B16F10 melanoma cells, MITF knockdown reduced expression of CXCL10, with concomitantly decreased attraction of immune cells and accelerated tumor outgrowth. Conversely, overexpression of MITF in YUMM1.1 melanoma cells also led to an increased immune cell attraction in vitro. Subcutaneous YUMM1.1 melanomas overexpressing MITF however showed a reduced immune infiltration of lymphocytes and an increased tumor growth. In human melanoma cell lines, silencing of MITF enhanced chemokine production and immune cell attraction, while overexpression of MITF led to lower immune cell attraction. In summary, our results show that MITF regulates chemokine expression in murine and in human melanoma cells, and affects in vivo immune cell attraction and tumor growth. These results reveal a functional relationship between MITF and immune cell infiltration, which may be exploited for cancer therapy.
Identifiants
pubmed: 30502589
pii: S1936-5233(18)30547-3
doi: 10.1016/j.tranon.2018.10.014
pmc: PMC6290759
pii:
doi:
Types de publication
Journal Article
Langues
eng
Pagination
350-360Informations de copyright
Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.
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