Premium
Development and characterization of efficient xenograft models for benign and malignant human prostate tissue
Author(s) -
Wang Yuzhuo,
Revelo Monica P.,
Sudilovsky Daniel,
Cao Mei,
Chen Wilfred G.,
Goetz Lester,
Xue Hui,
Sadar Marianne,
Shappell Scott B.,
Cunha Gerald R.,
Hayward Simon W.
Publication year - 2005
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.20225
Subject(s) - prostate , renal capsule , prostate cancer , medicine , pathology , androgen receptor , renal cell carcinoma , capsule , transplantation , cancer , biology , botany
BACKGROUND Various research groups have attempted to grow fresh, histologically intact human prostate cancer tissues in immunodeficient mice. Unfortunately, grafting of such tissues to the sub‐cutaneous compartment was found to be associated with low engraftment rates. Furthermore, xenografts could only be established using high‐grade, advanced stage, but not low‐ or moderate‐grade prostate cancer tissues. METHODS This paper describes methods for xenografting both benign and malignant human prostate tissue to severe combined immunodeficient (SCID) mice. We examine the efficiency and histopathologic consequences of grafting to the sub‐cutaneous, sub‐renal capsule, and prostatic orthotopic sites. RESULTS Sub‐renal capsule grafting was most efficient in terms of take rate (>90%) for both benign and malignant tissue. Orthotopic grafts consistently exhibited the best histopathologic differentiation, although good differentiation with continued expression of androgen receptors (AR) and PSA was also seen in the sub‐renal capsule site. Sub‐cutaneous grafting resulted in low take rates and the lowest level of histodifferentiation in surviving grafts. Grafted benign tissues in all sites appropriately expressed AR, PSA, cytokeratins 8, 18, and 14 as well as p63; carcinoma tissues did not express the basal cell markers. Grafting of tissues to castrated hosts did not affect the graft take rates (but was not practical in the case of the orthotopic site). Grafting followed by host castration resulted in epithelial regression with loss PSA and reduced AR expression at all three sites. CONCLUSIONS These data suggest that sub‐renal capsule and orthotopic grafting of human prostate tissue can be used for many basic scientific and translational studies. © 2005 Wiley‐Liss, Inc.