title: Coevolution of prostate cancer and bone stroma in three-dimensional coculture: implications for cancer growth and metastasis.
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 and metastasis.
authors.affiliation: Department of Urology, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
authors.forename: Shian-Ying
authors.initials: SY
authors.lastname: Sung
authors.forename: Chia-Ling
authors.initials: CL
authors.lastname: Hsieh
authors.forename: Andrew
authors.initials: A
authors.lastname: Law
authors.forename: Haiyen E
authors.initials: HE
authors.lastname: Zhau
authors.forename: Sen
authors.initials: S
authors.lastname: Pathak
authors.forename: Asha S
authors.initials: AS
authors.lastname: Multani
authors.forename: Sharon
authors.initials: S
authors.lastname: Lim
authors.forename: Ilsa M
authors.initials: IM
authors.lastname: Coleman
authors.forename: Li-Chin
authors.initials: LC
authors.lastname: Wu
authors.forename: William D
authors.initials: WD
authors.lastname: Figg
authors.forename: William L
authors.initials: WL
authors.lastname: Dahut
authors.forename: Peter
authors.initials: P
authors.lastname: Nelson
authors.forename: Jae K
authors.initials: JK
authors.lastname: Lee
authors.forename: Mahul B
authors.initials: MB
authors.lastname: Amin
authors.forename: Robert
authors.initials: R
authors.lastname: Lyles
authors.forename: Peter A J
authors.initials: PA
authors.lastname: Johnstone
authors.forename: Fray F
authors.initials: FF
authors.lastname: Marshall
authors.forename: Leland W K
authors.initials: LW
authors.lastname: Chung
mesh_terms: D000818:Animals; D001859:Bone Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000556:secondary*; D001842:Bone and Bones / Q000378:metabolism / Q000473:pathology* / Q000502:physiology; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D018925:Chemokines / Q000096:biosynthesis / Q000097:blood / Q000235:genetics; D018920:Coculture Techniques; D005109:Extracellular Matrix / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010006:Osteoblasts / Q000473:pathology; D012516:Osteosarcoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology / Q000502:physiology
chemical_list: D018925:Chemokines; D017382:Reactive Oxygen Species