Coevolution of prostate cancer and bone stroma in three-dimensional coculture: implications for cancer growth and metastasis.
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.
Sung
Shian-Ying
SY
Department of Urology, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
Hsieh
Chia-Ling
CL
Law
Andrew
A
Zhau
Haiyen E
HE
Pathak
Sen
S
Multani
Asha S
AS
Lim
Sharon
S
Coleman
Ilsa M
IM
Wu
Li-Chin
LC
Figg
William D
WD
Dahut
William L
WL
Nelson
Peter
P
Lee
Jae K
JK
Amin
Mahul B
MB
Lyles
Robert
R
Johnstone
Peter A J
PA
Marshall
Fray F
FF
Chung
Leland W K
LW
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
D018925:Chemokines; D017382:Reactive Oxygen Species