Establishment of short-term primary human prostate xenografts for the study of prostate biology and cancer

Human tissue xenograft models are currently the only tool for conducting in vivo analyses of intact human tissue. The goal of the present study was to develop reliable methods for successful generation of short-term primary t issue xenografts from benign and tumor-derived human prostate tissue. Prima ry human prostate xenografts were established in athymic nu/nu mice from ei ght of eight benign and five of five prostate cancer tissues, collected fro m a total of 10 patients who underwent radical prostatectomy for the treatm ent of prostate cancer. An average of 13 xenografts was established per spe cimen. Two tissue specimens were cryopreserved for >1 month before successf ul generation of prostate xenografts. After 1 mouth in vivo, xenograft tiss ues were harvested and examined regarding: gross evidence of vascularizatio n; tissue morphology; proliferation; apoptosis; and expression of androgen receptor, prostate-specific antigen, and high molecular weight cytokeratins specific for basal cells in the prostate. Direct comparison of the origina l tissue specimen and the 1-month xenografts revealed similar histology; si milar apoptotic and proliferative fractions in most cases; and comparable e xpression levels and expression patterns of androgen receptor, prostate-spe cific antigen, and high molecular weight cytokeratins. These data demonstra te that primary human prostate xenografts, benign and malignant, can be est ablished routinely from human prostate tissue surgical specimens, and that the xenografts maintain tissue architecture and expression of key prostatic markers. The development of this methodology, including the technique for cryopreservation of human tissue, will allow multiple (successive) analyses of human prostate tissue to be conducted throughout time using a tissue sa mple derived from a single patient; and simultaneous analysis of human pros tate tissues derived from a cohort of patients.