As stem cell biology and tumorigenesis are closely linked and as stem cells may have a role in the etiology of cancer we are currently defining features of normal prostate stem cells with the goal of determining if these are targets of transformation and if these have similar features to prostate cancer stem cells. We have shown that the proximal region of murine prostatic ducts is enriched in stem cells that express high levels of Sca-1, are quiescent and have high proliferative potential in vitro and in vivo. In addition, single proximal cells give rise to branched ductal structures that contain both basal and luminal cells. Cells from this region have significant regenerative capacity when assayed in an in vivo prostate reconstitution assay in which combinations of prostate cells and embryonic urogenital sinus mesenchyme (inductive mesenchyme for prostatic tissue) are inserted under the renal capsule of recipient animals. Proximal cells also withstand prolonged androgen deprivation, another characteristic of stem cells. Sca-1high prostate regenerating cells also express other antigens characteristic of stem cells such as alpha 6 integrin (~ 96%), and Bcl-2 (~ 80%). High levels of TGF-beta in the proximal region maintain the quiescence of the proximal stem cell niche. As we find that prostate stem cells reside within the population that expresses high levels of Sca-1 we determined the expression of Sca-1 on prostate cancer cells isolated from the prostate tumors of Pten deficient mice. We find these tumor cells express very high levels of Sca-1, indicating that cells expressing high levels of Sca-1 are expanded during tumorigenesis. Tumor cells with self-renewing and tumorigenic capacity reside exclusively in the Sca-1high population and are not present in the Sca-1medium/low and Sca-1negative populations. The data indicate that prostate tumor cells and normal prostate stem cells share common features and that normal stem cells are expanded during tumorigeneiss indicating that they are the likely target of carcinogenesis.
Professor, Department of Cell Biology
Professor, Department of Urology
Advsr - Cellular & Molecular Bio Instr. Hstlgy
Co Dir NCI Stem Cell Canc Cell Bio Trng Grant
Co Dir NY Stem Trng Grant Stem Cells
PhD from University of Cape Town
PLoS one. 2015; 10(5):e0128489-e0128489e0128489
Proceedings of the National Academy of Sciences of the United States of America (PNAS). 2013 Dec 17; 110(51):20611-20616
Prostate. 2012 Jun 15; 72(9):998-1005
PLoS one. 2010 Sep 30; 5(9):?-?
Science translational medicine. 2010 Aug 04; 2(43):43ps38-43ps38
Stem cells. 2009 Sep; 27(9):2220-2228
PLoS one. 2009 May 29; 4(5):e5722-e5722
Prostate. 2008 Sep 01; 68(12):1263-1272