Article

Prostate Cancer Cells with Stem Cell Characteristics Reconstitute the Original Human Tumor In vivo

Vanderbilt University, Нашвилл, Michigan, United States
Cancer Research (Impact Factor: 9.28). 06/2007; 67(10):4807-15. DOI: 10.1158/0008-5472.CAN-06-4608
Source: PubMed

ABSTRACT Cancer may arise from a cancer stem/progenitor cell that shares characteristics with its normal counterpart. We report the reconstitution of the original human prostate cancer specimen from epithelial cell lines (termed HPET for human prostate epithelial/hTERT) derived from this sample. These tumors can be described in terms of Gleason score, a classification not applied to any of the transgenic mouse models currently developed to mimic human disease. Immunohistochemical and Western blot analyses indicate that they do not express androgen receptor or p63, similar to that reported for prostate stem cells. These cell lines also express embryonic stem markers (Oct4, Nanog, and Sox2) as well as early progenitor cell markers (CD44 and Nestin) in vitro. Clonally derived HPET cells reconstitute the original human tumor in vivo and differentiate into the three prostate epithelial cell lineages, indicating that they arise from a common stem/progenitor cell. Serial transplantation experiments reconstitute the tumors, suggesting that a fraction of parental or clonally derived HPET cells have self-renewal potential. Thus, this model may enhance our understanding of human tumor development and provide a mechanism for studying cancer stem/progenitor cells in differentiation, tumorigenesis, preclinical testing, and the development of drug resistance.

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    • "In addition, BMI1 activates Akt and hTERT (telomerase reverse transcriptase) via PTEN phosphatase repression [130]. Interestingly, Akt and hTERT are required for PCa CRC self-renewal [62] [131]. The pathways regulated by BMI1 suggest that the maintenance of PCa CRC critically depends on BMI1 integrity. "
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    • "It is widely accepted that adult stem cells are involved in normal tissue replenishment throughout life while cancer stem cells support cancer growth (Presnell et al., 2002, Smith et al., 2007). Although the cell(s) of origin for prostate cancer may include luminal, basal, neuroendocrine, progenitor and stem cells (Kasper, 2008, Wang et al., 2009), it is increasingly evident that the resultant prostate cancers contain cancer stem cells that continuously seed and maintain tumor growth (Gu et al., 2007, Kasper, 2008, Kasper, 2009). Even though conventional therapies for prostate cancer eradicate the majority of cells within a tumor, most patients with advanced cancer eventually progress to androgen-independent, metastatic disease that remains essentially incurable by current treatment strategies. "
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    • "Different systems have been used to culture PCSCs, including using suspension, low adherence culture on a layer of agar [16] [18], or use of low adherence plates [17] [20]. In general, two types of media are used to culture these stem-like PC cells that contained either fetal bovine serum (FBS) [17] [19], or supplemented with epidermal growth factor (EGF; 10 or 20 ng/ml) and basic fibroblast growth factor (bFGF; 10 or 20 ng/ml) [16] [20]. Although these stem-like PC cells have been demonstrated to have CSC properties, these cells have not been cultured for an extended period of time. "
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