Endogenous Production of IL1B by Breast Cancer Cells Drives Metastasis and Colonization of the Bone Microenvironment.
Aged
Animals
Apoptosis
Bone Neoplasms
/ genetics
Breast Neoplasms
/ genetics
Case-Control Studies
Cell Proliferation
Epithelial-Mesenchymal Transition
Female
Follow-Up Studies
Gene Expression Regulation, Neoplastic
Humans
Interleukin-1beta
/ genetics
Mice
Mice, Inbred NOD
Mice, SCID
Middle Aged
Prognosis
Tumor Cells, Cultured
Tumor Microenvironment
Xenograft Model Antitumor Assays
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 05 2019
01 05 2019
Historique:
received:
11
07
2018
revised:
20
11
2018
accepted:
17
01
2019
pubmed:
24
1
2019
medline:
20
6
2020
entrez:
24
1
2019
Statut:
ppublish
Résumé
Breast cancer bone metastases are incurable, highlighting the need for new therapeutic targets. After colonizing bone, breast cancer cells remain dormant, until signals from the microenvironment stimulate outgrowth into overt metastases. Here we show that endogenous production of IL1B by tumor cells drives metastasis and growth in bone. Tumor/stromal IL1B and IL1 receptor 1 (IL1R1) expression was assessed in patient samples and effects of the IL1R antagonist, Anakinra, or the IL1B antibody canakinumab on tumor growth and spontaneous metastasis were measured in a humanized mouse model of breast cancer bone metastasis. Effects of tumor cell-derived IL1B on bone colonization and parameters associated with metastasis were measured in MDA-MB-231, MCF7, and T47D cells transfected with In tissue samples from >1,300 patients with stage II/III breast cancer, IL1B in tumor cells correlated with relapse in bone (HR = 1.85; 95% CI, 1.05-3.26; Pharmacologic inhibition of IL1B has potential as a novel treatment for breast cancer metastasis.
Identifiants
pubmed: 30670488
pii: 1078-0432.CCR-18-2202
doi: 10.1158/1078-0432.CCR-18-2202
doi:
Substances chimiques
IL1B protein, human
0
Interleukin-1beta
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2769-2782Subventions
Organisme : Medical Research Council
ID : MR/P000096/1
Pays : United Kingdom
Informations de copyright
©2019 American Association for Cancer Research.