RANKLed by the Complexity of Signaling in Breast Cancer Metastasis to the Brain.
Brain
Breast cancer
Metastasis
RANK
RANKL
Journal
Clinical breast cancer
ISSN: 1938-0666
Titre abrégé: Clin Breast Cancer
Pays: United States
ID NLM: 100898731
Informations de publication
Date de publication:
10 2020
10 2020
Historique:
received:
19
01
2020
revised:
17
03
2020
accepted:
01
04
2020
pubmed:
10
5
2020
medline:
3
11
2021
entrez:
9
5
2020
Statut:
ppublish
Résumé
Receptor activator of nuclear factor κB (RANK) and its ligand, RANKL, are essential for mammary gland development and play a vital role in breast carcinogenesis. RANKL-RANK signaling also drives thermoregulation and modulates inflammatory activation in the brain. The expression of RANKL in primary breast cancer (BC) has been negatively associated with brain metastases, while significantly higher levels of RANK are seen in BC with brain metastases. We examined the expression of RANK and RANKL in BC metastasis to the brain. We examined the expression of RANK and RANKL in 40 cases of BC metastasis to the brain. RANK was variably expressed in BC cells but minimally expressed in the adjacent brain parenchyma. In contrast, the expression of RANKL was minimal in metastatic BC but highly variable in tumoral stroma. RANKL expression in normal brain stroma obtained during autopsy was negligible. Histologic grade and BC subtypes were not significantly associated with RANK expression in metastatic BC. A significant negative correlation between RANK in metastatic BC and RANKL in tumoral stroma was identified (P < .001). RANK expressed by primary BC and RANKL detected in the tumor microenvironment together participate in cancer development, while the same principle may operate at distant sites. Further investigation is necessary to provide additional insight into the role of the RANKL-RANK pathway in BC progression and to investigate the potential efficacy of therapeutic strategies targeting these molecules in BC metastasis to the brain.
Sections du résumé
BACKGROUND
Receptor activator of nuclear factor κB (RANK) and its ligand, RANKL, are essential for mammary gland development and play a vital role in breast carcinogenesis. RANKL-RANK signaling also drives thermoregulation and modulates inflammatory activation in the brain. The expression of RANKL in primary breast cancer (BC) has been negatively associated with brain metastases, while significantly higher levels of RANK are seen in BC with brain metastases. We examined the expression of RANK and RANKL in BC metastasis to the brain.
PATIENTS AND METHODS
We examined the expression of RANK and RANKL in 40 cases of BC metastasis to the brain.
RESULTS
RANK was variably expressed in BC cells but minimally expressed in the adjacent brain parenchyma. In contrast, the expression of RANKL was minimal in metastatic BC but highly variable in tumoral stroma. RANKL expression in normal brain stroma obtained during autopsy was negligible. Histologic grade and BC subtypes were not significantly associated with RANK expression in metastatic BC. A significant negative correlation between RANK in metastatic BC and RANKL in tumoral stroma was identified (P < .001).
CONCLUSION
RANK expressed by primary BC and RANKL detected in the tumor microenvironment together participate in cancer development, while the same principle may operate at distant sites. Further investigation is necessary to provide additional insight into the role of the RANKL-RANK pathway in BC progression and to investigate the potential efficacy of therapeutic strategies targeting these molecules in BC metastasis to the brain.
Identifiants
pubmed: 32381383
pii: S1526-8209(20)30071-9
doi: 10.1016/j.clbc.2020.04.001
pii:
doi:
Substances chimiques
RANK Ligand
0
Receptor Activator of Nuclear Factor-kappa B
0
TNFRSF11A protein, human
0
TNFSF11 protein, human
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e569-e575Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.