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Antiestrogens are effective in the treatment of metastatic prostate cancer. However, the mechanism is not completely understood. We have used a three-dimensional in situ organotypic culture of human tissue to examine the differential effects of antiestrogens on cell proliferation, motility and invasion and on the growth of tumors with and without antiestrogens in vivo. Cell proliferation, motility and invasion were examined in human PC-3 and VCaP cells in tissue culture and in PC-3 xenografts in nude mice treated with antiestrogens or control. Proliferation was examined in organotypic cultures of human tissue using Ki-67 immunostaining. Cell invasion and motility were examined in two-dimensional cell culture using Transwell and wound-closure assays. The effects of antiestrogens on tumor growth were examined in PC-3 xenografts in nude mice treated with antiestrogens or control. There was a significant increase in tumor growth, proliferation and motility in the presence of antiestrogens in vivo. However, antiestrogens had only a modest effect on cell proliferation, motility or invasion in vitro. Cell proliferation, motility and invasion were increased in the presence of antiestrogens in tumors with antiestrogens in vivo. Cell proliferation was not increased in control tumors with antiestrogens, but there was a significant increase in motility and invasion in the presence of antiestrogens in tumors without antiestrogens in vivo. Furthermore,
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