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Experimental Prostate Epithelial Morphogenesis in Response to Stroma and Three-Dimensional Matrigel Culture¹

YCR Cancer Research Unit [S. H. L., N. J. M.], Department of Biology [M. S.], University of York, Heslington, York YO10 5YW; Prostate Research Group, Department of Surgery, The Medical School, University of Newcastle, Newcastle Upon Tyne NE2 4HH, United Kingdom [A. C.]; Pyrah Department of Urology, St. James Hospital, Leeds LS9 7TF [A. B. P.]; and Department of Urology, York District Hospital, York YO31 8HE [M. J. S.], United Kingdom

To reproduce the structural and functional differentiation of human prostatic acini in vivo, prostatic epithelial and stromal cells derived from human primary cultures were cocultured in Matrigel. In the absence of stroma and serum, epithelial spheroids composed of solid masses of stratified and cuboidal cells formed. Outer cells of the spheroid expressed cytokeratins 1, 5, 10, and 14, whereas the inner cells expressed cytokeratin 18. The addition of 2% serum induced formation of a lumen surrounded by a layer of one or two cuboidal and columnar epithelial cells. The further addition of stromal cultures, dihydrotestosterone, and estrogen induced polarization of the epithelium and increased spheroid-forming efficiency. Epithelium expressed either cytokeratin 18 alone or additionally cytokeratins 1, 5, 14, and 10. All spheroid epithelium expressed prostate-specific antigen and prostate-specific membrane antigen. Androgen receptor was only detected in the presence of stroma, serum, and hormones. Thus, development of a functional and morphologically correct prostate gland in vitro is dependent on extracellular matrix, steroid hormones, and factors from stromal cells and serum.

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