Prospective identification of tumorigenic prostate cancer stem cells.
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+/alpha2beta1hi/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+/alpha2beta1hi/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.
Collins
Anne T
AT
Yorkshire Cancer Research Unit, Department of Biology, University of York, York, United Kingdom. ac43@york.ac.uk
Berry
Paul A
PA
Hyde
Catherine
C
Stower
Michael J
MJ
Maitland
Norman J
NJ
D000071916:AC133 Antigen; D000368:Aged; D015703:Antigens, CD / Q000096:biosynthesis; D002454:Cell Differentiation / Q000502:physiology; D048708:Cell Growth Processes / Q000502:physiology; D006023:Glycoproteins / Q000096:biosynthesis; D006801:Humans; D018960:Hyaluronan Receptors / Q000096:biosynthesis; D038982:Integrin alpha2beta1 / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology*; D010455:Peptides; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D011944:Receptors, Androgen / Q000096:biosynthesis
D000071916:AC133 Antigen; D015703:Antigens, CD; C497483:CD44 protein, human; D006023:Glycoproteins; D018960:Hyaluronan Receptors; D038982:Integrin alpha2beta1; C000606023:PROM1 protein, human; D010455:Peptides; D011944:Receptors, Androgen