PROSTATE EPITHELIAL STEM CELL
LAY REVIEW

The advancement of stem cell research led to the emergence of a new model that proposed dysfunctional stem cells or de-differentiation of progenitor cells that lead to cancers [1, 5]. Research leading to the elucidation of factors influencing prostate stem cell proliferation and differentiation may open doors to finding new treatments for prostate diseases.

The human prostate surrounds the urethra and is located between the bladder and the rectum [2]. It is a small, partly glandular and partly muscular body about the size and shape of a chestnut and is wrapped in a band of smooth muscle cells which secrete factors necessary for proper prostate development [3, 8]. The gland is made up of several follicular pouches which join to form excretory ducts and open into canals where seminal fluid created is drained into the urethra [2]. Although it is currently unknown where prostate epithelial stem cells reside, they are believed to exist predominantly in the region nearest to the urethra, with partially differentiated stem cells residing throughout the remaining areas of the gland [4].

Prostate development begins in utero with ductal budding beginning approximately ten weeks after gestation [1]. The prostate continues to grow up to one year after birth, followed by a period of dormancy until puberty, where further growth occurs in response to an increase in testosterone [1]. Five different cell types can be found in the mature prostate: prostate epithelial stem cells, basal epithelial cells, transit-amplifying cells, secretory luminal cells and neuroendocrine cells [5]. Prostate epithelial stem cells aside, it is thought that basal epithelial cells are more stem-like in nature compared to other cells in the prostate gland and that transit-amplifying cells represent the intermediate stage of differentiation of a basal epithelial cell into either a secretory luminal or neuroendocrine cell [5].

The survival of secretory luminal cells relies heavily on androgen [1]. Research has shown that castration of adult male rats, which are androgen-deprived for several years after castration, will remain so [1]. Upon re-administration of androgen, the prostate gland can be fully restored [1]. This ability to restore the prostate is thought to be due to the survival of both androgen-independent basal epithelial cells and stem cells [1].

In the United States, prostate cancer is the second leading cancer-related cause of death in men with a 10% mortality rate for those diagnosed with the disease [2]. It is estimated that 235,000 American men will be diagnosed with prostate cancer in 2006 [2]. Age, diet, genetics and nationality have all been shown to be risk factors for developing the disease [2]. Prostate cancer is believed to be a disorder of cell differentiation and cell proliferation [7], thus, research to further our understanding of prostate stem cell differentiation could lead to the discovery of novel treatments against the disease.

References:

1. Collins AT, Maitland NJ (2006) Prostate cancer stem cells. Eur J Cancer 42:1213-18.
2. Early Prostate Cancer: Questions and Answers. National Cancer Institute. 31 Oct 2006. <http://www.cancer.gov/cancertopics/factsheet/Detection/early-prostate>.

1. Gray, Henry. Gray’s Anatomy, 15th Edition. Barnes & Noble Books, 1995: 993-995.
2. Goto K, Salm SN, Coetzee S, Xiong X, Burger P, Shapiro E, Lepor H, Moscatelli D, Wilson EL (2006) Proximal prostatic stem cells are programmed to regenerate a proximal-distal ductal axis. Stem Cells 24:1859-68.
3. Lam JS, Reither RE (2006) Stem cells in prostate and prostate cancer development. Urologic Oncol: Sem and Original Invest 24:131-40.
4. Richardson GD, Robson CN, Lang SH, Neal DE, Maitland NJ, Collins AT (2004) CD133, a novel marker for human prostatic epithelial stem cells. J Cell Sci 117:3539-45.
5. Schmelz M, Moll R, Hesse U, Prasad AR, Gandolfi JA, Hasan SR, Bartholdi M, Cress AE (2005) Identification of a stem cell candidate in the normal prostate gland. Eur J Cell Biol 84:341-54.
6. Signoretti S, Loda M (2007) Prostate stem cells: From development to cancer. Sem Cancer Biol 17:219-24.
7. Tsujimura A, Koikawa Y, Salm S, Takao T, Coetzee S, Moscatelli D, Shapiro E, Lepor H, Sun T, Wilson EL (2002) Proximal location of mouse prostate epithelial stem cells: a model of prostatic homeostasis. J Cell Biol 157:1257-65.