Establishment of a three-dimensional human prostate organoid coculture under microgravity-simulated conditions: Evaluation of androgen-induced growth and psa expression |
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Authors: | Haiyen E Zhau Thomas J Goodwin Shi-Ming Chang Tacey L Baker Leland W K Chung |
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Affiliation: | (1) Molecular Urology and Therapeutics Program, Box 422, Department of Urology, University of Virginia, 22908 Charlottesville, Virginia;(2) NASA Johnson Space Center, 77058 Houston, Texas |
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Abstract: | Summary A novel in vitro human prostate cancer model was established by using a coculture technique in which isolated human prostate fibroblasts were
observed to grow as a mixed culture with isolated human prostate cancer cells (LNCaP) on microcarrier beads under microgravity-simulated
conditions. This model appears to be promising and deserves further exploration because: (a) cocultured human prostate fibroblasts
and cancer epithelial cells appear to undergo patterns of histogenesis similar to those observed in human prostate tumors
and (b) unlike the conventional cell culture on plastic dishes, cocultured human prostate fibroblasts and LNCaP cells in microgravity-simulated
conditions responded to the inductive signals of growth and differentiation from dihydrotestosterone in a manner similar to
that observed in the in vivo condition. These results offer an opportunity to examine molecular mechanisms of cellular signaling in response to androgen
stimulation during normal and aberrant human prostate development. The microgravity-simulated three-dimensional prostate epithelial
cell culture with prostate fibroblasts can be further explored as an ideal in vitro model for the study of normal and neoplastic prostate development. This model could also be adopted as a drug screening program
for the discovery of novel therapeutic agents in the treatment of human prostate cancer and benign hyperplastic growth. |
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Keywords: | stromal-epithelial interaction microgravity-simulated prostate cell culture three-dimensional prostate cell culture dihydrotesterone-induced prostate cancer growth and differentiation prostate-specific antigen expression |
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