Bone-in-culture array as a platform to model early-stage bone metastases and discover anti-metastasis therapies

Hai Wang, Lin Tian, Amit Goldstein, Jun Liu, Hin Ching Lo, Kuanwei Sheng, Thomas Welte, Stephen T.C. Wong, Zbigniew Gugala, Fabio Stossi, Chenghang Zong, Zonghai Li, Michael A. Mancini, Xiang H.F. Zhang

Research output: Contribution to journalArticle

6 Scopus citations

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.

Original languageEnglish (US)
Article number15045
JournalNature communications
Volume8
DOIs
StatePublished - Jan 1 2017

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ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Wang, H., Tian, L., Goldstein, A., Liu, J., Lo, H. C., Sheng, K., Welte, T., Wong, S. T. C., Gugala, Z., Stossi, F., Zong, C., Li, Z., Mancini, M. A., & Zhang, X. H. F. (2017). Bone-in-culture array as a platform to model early-stage bone metastases and discover anti-metastasis therapies. Nature communications, 8, [15045]. https://doi.org/10.1038/ncomms15045