Coevolution of prostate cancer and bone stroma in three-dimensional coculture: Implications for cancer growth and metastasis

Shian Ying Sung, Chia Ling Hsieh, Andrew Law, Haiyen E. Zhau, Sen Pathak, Asha S. Multani, Sharon Lim, Ilsa M. Coleman, Li Chin Wu, William D. Figg, William L. Dahut, Peter Nelson, Jae K. Lee, Mahul B. Amin, Robert Lyles, Peter A.J. Johnstone, Fray F. Marshall, Leland W.K. Chung

Research output: Contribution to journalArticlepeer-review

132 Scopus citations

Abstract

Human bone stromal cells, after three-dimensional coculture with human prostate cancer (PCa) cells in vitro, underwent permanent cytogenetic and gene expression changes with reactive oxygen species serving as mediators. The evolved stromal cells are highly inductive of human PCa growth in mice, and expressed increased levels of extracellular matrix (versican and tenascin) and chemokine (BDFN, CCL5, CXCL5, and CXCL16) genes. These genes were validated in clinical tissue and/or serum specimens and could be the predictors for invasive and bone metastatic PCa. These results, combined with our previous observations, support the concept of permanent genetic and behavioral changes of PCa epithelial cells after being either cocultured with prostate or bone stromal cells as three-dimensional prostate organoids or grown as tumor xenografts in mice. These observations collectively suggest coevolution of cancer and stromal cells occurred under three-dimensional growth condition, which ultimately accelerates cancer growth andmetastasis.

Original languageEnglish
Pages (from-to)9996-10003
Number of pages8
JournalCancer Research
Volume68
Issue number23
DOIs
StatePublished - 1 Dec 2008
Externally publishedYes

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