Development and characterization of efficient xenograft models for benign and malignant human prostate tissue
- PMID: 15678503
- DOI: 10.1002/pros.20225
Development and characterization of efficient xenograft models for benign and malignant human prostate tissue
Abstract
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.
(c) 2005 Wiley-Liss, Inc.
Comment in
-
Next generation patient-derived prostate cancer xenograft models.Asian J Androl. 2014 May-Jun;16(3):407-12. doi: 10.4103/1008-682X.125394. Asian J Androl. 2014. PMID: 24589467 Free PMC article.
Similar articles
-
Conversion from a paracrine to an autocrine mechanism of androgen-stimulated growth during malignant transformation of prostatic epithelial cells.Cancer Res. 2001 Jul 1;61(13):5038-44. Cancer Res. 2001. PMID: 11431338
-
Establishing prostate cancer patient derived xenografts: lessons learned from older studies.Prostate. 2015 May;75(6):628-36. doi: 10.1002/pros.22946. Epub 2015 Jan 5. Prostate. 2015. PMID: 25560784 Free PMC article.
-
Role of canine basal cells in prostatic post natal development, induction of hyperplasia, sex hormone-stimulated growth; and the ductal origin of carcinoma.Prostate. 2001 May 15;47(3):149-63. doi: 10.1002/pros.1058. Prostate. 2001. Corrected and republished in: Prostate. 2001 Aug 1;48(3):210-24. doi: 10.1002/pros.1100. PMID: 11351344 Corrected and republished.
-
Differentiation pathways and histogenetic aspects of normal and abnormal prostatic growth: a stem cell model.Prostate. 1996 Feb;28(2):98-106. doi: 10.1002/(SICI)1097-0045(199602)28:2<98::AID-PROS4>3.0.CO;2-J. Prostate. 1996. PMID: 8604398 Review.
-
Human benign prostatic hyperplasia heterotransplants as an experimental model.Asian J Androl. 2010 Mar;12(2):157-63. doi: 10.1038/aja.2009.77. Epub 2009 Nov 30. Asian J Androl. 2010. PMID: 19946317 Free PMC article. Review.
Cited by
-
PDX: Moving Beyond Drug Screening to Versatile Models for Research Discovery.J Endocr Soc. 2020 Sep 12;4(11):bvaa132. doi: 10.1210/jendso/bvaa132. eCollection 2020 Nov 1. J Endocr Soc. 2020. PMID: 33094211 Free PMC article. Review.
-
Patient-derived xenograft (PDX) models, applications and challenges in cancer research.J Transl Med. 2022 May 10;20(1):206. doi: 10.1186/s12967-022-03405-8. J Transl Med. 2022. PMID: 35538576 Free PMC article. Review.
-
Patient-derived tissue slice grafts accurately depict response of high-risk primary prostate cancer to androgen deprivation therapy.J Transl Med. 2013 Aug 28;11:199. doi: 10.1186/1479-5876-11-199. J Transl Med. 2013. PMID: 23985008 Free PMC article.
-
Using PDX for Preclinical Cancer Drug Discovery: The Evolving Field.J Clin Med. 2018 Mar 2;7(3):41. doi: 10.3390/jcm7030041. J Clin Med. 2018. PMID: 29498669 Free PMC article. Review.
-
A preclinical xenograft model of prostate cancer using human tumors.Nat Protoc. 2013 May;8(5):836-48. doi: 10.1038/nprot.2013.043. Epub 2013 Apr 4. Nat Protoc. 2013. PMID: 23558784
Publication types
MeSH terms
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Research Materials
Miscellaneous