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Coevolution of Prostate Cancer and Bone Stroma in Three-Dimensional Coculture: Implications for Cancer Growth and Metastasis

Departments of ¹ Urology, ² Radiation Oncology, and ³ Pathology, Emory University School of Medicine, ⁴ Department of Biostatistics and Bioinformatics, Emory University Rollin School of Public Health, Atlanta, Georgia; ⁵ Department of Molecular Genetics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas; Departments of ⁶ Urology and ⁷ Public Health Sciences, University of Virginia, Charlottesville, Virginia; ⁸ Fred Hutchinson Cancer Center, Seattle, Washington; ⁹ Center for Cancer Research, National Cancer Institute, Bethesda, Maryland; ¹⁰ Center for Molecular Medicine and Graduate Institute of Cancer Biology, China Medical University and Hospital, Taichung, Taiwan, ROC; and ¹¹ Department of Biotechnology, Asia University, Wufeng, Taichung, Taiwan, ROC

Requests for reprints: Leland W. K. Chung, Molecular Urology and Therapeutics Program, Department of Urology, Emory University School of Medicine, 1365B Clifton Road, Room B5101, Atlanta, GA 30322. Phone: 404-778-3672; Fax: 404-778-778-3965; E-mail: lwchung{at}emory.edu.

Key Words: reciprocal stromal-epithelial interaction • plasticity of tumor and stroma • induction of permanent genetic and behavior changes • tumor microenvironment • prostate cancer cells • bone and prostate stromal cells • LN • MG63 • HS27A • serum PSA • luciferase • Tenascin • Versican • BDNF • CCL5 • CXCL5 and CXCL16

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 and metastasis. [Cancer Res 2008;68(23):9996–10003]

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				Correction: Tumor-Stroma Interactions in the Prostate Cancer Res., January 15, 2009; 69(2): 721 - 721. [Full Text] [PDF]