Bone-in-culture array as a platform to model early-stage bone metastases and discover anti-metastasis therapies.
Nat Commun
; 8: 15045, 2017 04 21.
Article
em En
| MEDLINE
| ID: mdl-28429794
ABSTRACT
The majority of breast cancer models for drug discovery are based on orthotopic or subcutaneous tumours. Therapeutic responses of metastases, especially microscopic metastases, are likely to differ from these tumours due to distinct cancer-microenvironment crosstalk in distant organs. Here, to recapitulate such differences, we established an ex vivo bone metastasis model, termed bone-in-culture array or BICA, by fragmenting mouse bones preloaded with breast cancer cells via intra-iliac artery injection. Cancer cells in BICA maintain features of in vivo bone micrometastases regarding the microenvironmental niche, gene expression profile, metastatic growth kinetics and therapeutic responses. Through a proof-of-principle drug screening using BICA, we found that danusertib, an inhibitor of the Aurora kinase family, preferentially inhibits bone micrometastases. In contrast, certain histone methyltransferase inhibitors stimulate metastatic outgrowth of indolent cancer cells, specifically in the bone. Thus, BICA can be used to investigate mechanisms involved in bone colonization and to rapidly test drug efficacies on bone micrometastases.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Pirazóis
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Benzamidas
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Osso e Ossos
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Neoplasias Ósseas
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Inibidores de Proteínas Quinases
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Aurora Quinases
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Antineoplásicos
Limite:
Animals
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Female
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Humans
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article