Prospective identification of tumorigenic prostate cancer stem cells

AT Collins, PA Berry, C Hyde, MJ Stower, NJ Maitland - Cancer research, 2005 - AACR
AT Collins, PA Berry, C Hyde, MJ Stower, NJ Maitland
Cancer research, 2005AACR
Existing therapies for prostate cancer eradicates the bulk of cells within a tumor. However,
most patients go on to develop androgen-independent disease that remains incurable by
current treatment strategies. There is now increasing evidence in some malignancies that
the tumor cells are organized as a hierarchy originating from rare stem cells that are
responsible for maintaining the tumor. We report here the identification and characterization
of a cancer stem cell population from human prostate tumors, which possess a significant …
Abstract
Existing therapies for prostate cancer eradicates the bulk of cells within a tumor. However, most patients go on to develop androgen-independent disease that remains incurable by current treatment strategies. There is now increasing evidence in some malignancies that the tumor cells are organized as a hierarchy originating from rare stem cells that are responsible for maintaining the tumor. We report here the identification and characterization of a cancer stem cell population from human prostate tumors, which possess a significant capacity for self-renewal. These cells are also able to regenerate the phenotypically mixed populations of nonclonogenic cells, which express differentiated cell products, such as androgen receptor and prostatic acid phosphatase. The cancer stem cells have a CD44+2β1hi/CD133+ phenotype, and we have exploited these markers to isolate cells from a series of prostate tumors with differing Gleason grade and metastatic states. Approximately 0.1% of cells in any tumor expressed this phenotype, and there was no correlation between the number of CD44+2β1hi/CD133+ cells and tumor grade. The identification of a prostate cancer stem cell provides a powerful tool to investigate the tumorigenic process and to develop therapies targeted to the stem cell.
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