Elaine L. Wilson, Ph.D.

Associate Professor of Cell Biology and Urology
Departments of Cell Biology and Urology

Research summary

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-1 high 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 that 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 tumorigenesis, indicating that they are the likely target of carcinogenesis.