Evidence of pluripotent human prostate stem cells in a human prostate primary xenograft model

Huss, Wendy J.; Gray, Danny R.; Werdin, Eric S.; Funkhouser, William K.; Smith, Gary J.

doi:10.1002/pros.20041

Cited by 43 publications

(35 citation statements)

References 41 publications

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“…Therefore, the heterotransplanted tumor, in the first passage, always showed a histopathological pattern typical of human prostate carcinoma. This fidelity has been demonstrated for well-differentiated, moderately differentiated and poorly differentiated carcinomas, as well as metastatic tumors that are moderately to poorly differentiated [14][15][16][17][18][19][20][21][22][23][24][25][26][27][28]. Similar results were obtained with poorly differentiated primary carcinomas when the implantation site was the renal subcapsule [29].…”

Section: Histological Analysissupporting

confidence: 55%

“…Remarkably, differentiated tumors do not become anaplastic but remain differentiated once heterotransplanted into the host mice [30,31]. In addition, the heterotransplanted tumors have a Gleason score identical to the original biopsy [27,32]. However, the heterotransplants possess little stroma that, histologically, seems derived from the host mouse [18].…”

Section: Histological Analysismentioning

confidence: 99%

“…However, the heterotransplants possess little stroma that, histologically, seems derived from the host mouse [18]. Notably, the histology of the human prostate tumor is preserved in the heterotransplant, even when the tissue is cryopreserved before transplantation [27,32]. These results have been found regardless of the mouse strain used (athymic nude, severe combined immunosuppressed mice [scid], or hpg/hpg or hpg/− scid mice [gonadal steroid-deficient mice]) [33], the coinjection of tumor tissue with Matrigel (BectonDickinson, Franklin Lakes, NJ, USA), or the use of intact or orchiectomized mice treated with androgen supplements.…”

Section: Histological Analysismentioning

confidence: 99%

“…In both cases, hormonal supplementation with T-pellets is advantageous. When the original tissue was cryopreserved before implantation, the tumor take rate was reduced compared with heterotransplants implanted from fresh tissue [27].…”

Section: Tumor Take Ratementioning

confidence: 99%

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Human prostate cancer heterotransplants: a review on this experimental model

López-Barcons¹

2010

Asian J Androl

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A common model used for preclinical research was in vitro human tumor cell culture. An alternative model was the direct implantation of a unique patient's tumor biopsy specimens into immunodeficient host mice. Published data from PubMed (http://www.ncbi.nlm.nih.gov) and Current Contents Connect databases (http://thomsonreuters.com/ products_services/science/science_products/a-z/current_contents_connect) were reviewed. Prostate cancer (PCa) heterotransplantation was evaluated using histopathology, morphology, cell differentiation, DNA content, tumor marker expression, metastases, tumor kinetics, tumor take rate and tumor vasculature in the first tumor heterotransplant. The heterotransplanted tumor retained the biological properties of the original tumor, such as morphology, degree of differentiation, pathology, secretory activity, expression of tumor markers and human vasculature. Human PCa heterotransplants have considerable experimental advantages over cell culture following xenotransplantation.

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Section: Histological Analysissupporting

confidence: 55%

Section: Histological Analysismentioning

confidence: 99%

Section: Histological Analysismentioning

confidence: 99%

Section: Tumor Take Ratementioning

confidence: 99%

See 2 more Smart Citations

Human prostate cancer heterotransplants: a review on this experimental model

López-Barcons¹

2010

Asian J Androl

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“…In a human prostate primary xenograft model developed in our laboratory, the response of putative prostate stem cells and tumor stem cells to androgen deprivation was characterized in xenografts transplanted into athymic nu/nu mice (12,13). Prostate stem/progenitor cells in the xenografts survived androgen deprivation and maintained pluripotentiality, as shown by their capacity to generate progeny that differentiated along multiple lineages in response to inductive microenvironmental signals (13).…”

Section: Introductionmentioning

confidence: 99%

Breast Cancer Resistance Protein–Mediated Efflux of Androgen in Putative Benign and Malignant Prostate Stem Cells

et al. 2005

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Malignantly transformed stem cells represent a potential common nidus for the primary cancer and the recurrent cancer that arises after treatment failure. Putative prostate stem cells and prostate tumor stem cells in benign and malignant human prostate tissue, in primary human prostate xenografts, and in the transgenic adenocarcinoma of the mouse prostate (TRAMP) mouse model of prostate cancer, are defined by expression of breast cancer resistance protein (BCRP), a marker of pluripotent hematopoietic, muscle, and neural stem cells, and by an absence of androgen receptor (AR) protein. Inhibition of BCRP-mediated efflux of dihydrotestosterone by novobiocin or fumitremorgin C in a rat prostate progenitor cell line that expresses BCRP and AR mRNAs, but minimal AR protein, results in stabilization and nuclear translocation of AR protein, providing a mechanism for lack of AR protein in BCRP-expressing stem cells. In both benign and malignant human prostate tissue, the rare epithelial cells that express BCRP and lack AR protein are localized in the basal cell compartment, survive androgen deprivation, and maintain proliferative potential in the hypoxic, androgen-deprived prostate. Putative prostate tumor stem cells that express BCRP but not AR protein in TRAMP are the source of a BCRP-negative and AR-negative, Foxa2-and SV40Tag-expressing, transit amplifying compartment that progresses to the poorly differentiated carcinomas that arise rapidly after castration. Therefore, BCRP expression isolates prostate stem/tumor stem cells from the prostate tissue microenvironment through constitutive efflux of androgen, protecting the putative tumor stem cells from androgen deprivation, hypoxia, or adjuvant chemotherapy, and providing the nidus for recurrent prostate cancer. (Cancer Res 2005; 65(15): 6640-50)

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