Using Human Prostate Epithelial Cells to Understand Prostate Cancer

Did you know that 1 in 7 men will be diagnosed with prostate cancer in their lifetime? Prostate cancer is the second most common cancer diagnosis and the second leading cause of cancer-related deaths in elderly men in the US. The good news, though, is that if caught and treated early, the chance of survival is pretty high. However, early diagnosis is difficult as men show few if any symptoms at the beginning stages of prostate cancer.

Scientists are working hard to understand the biology of the male prostate and how healthy prostate tissue can develop into cancer in hopes of providing ways for early detection and treatment of this disease. The easiest way to do this is to study prostate cancer cells and compare them to healthy prostate cells in vitro.

The male prostate is composed of numerous small glands that are lined with secretory epithelial cells. In prostate cancer, these epithelial cells (there are three types: luminal, basal, and neuroendocrine) can acquire genetic mutations that transform them into cancer cells. Therefore, prostate epithelial cells are ideal models to study normal prostate function and the pathogenesis of prostate cancer.

Two recent publications highlight the importance of conducting prostate cancer research using validated normal Human Prostate Epithelial Cells (HPrEC) from Lifeline Cell Technology®.

The first study by Zhang et al. was interested in understanding the formation of prostate organoids in culture (1). Using our normal Human Prostate Epithelial Cells, they demonstrated that these cells expressed the luminal markers — cytokeratins 8/18 — and basal markers — cytokeratin 5/14 — as well as the androgen receptor, and the prostate stem cell antigen. Further analysis revealed that these cells were CD133^–CD44⁺ α2β1 integrin⁺, which is characteristic of transit amplifying, intermediate prostate epithelial cells. They also found that HPrECs plated on matrigel differentiated into 3D organoids that contained spherical acinar structures with tubules extending into the cell culture media. These structures closely resemble characteristics of prostate development. Using our HPrEC-derived organoids, the authors concluded that two genes, CEACAM1 and CEACAM20, which are down-regulated in prostate cancer, are essential to lumen formation of normal prostate tissue and for in vitrogeneration of 3D prostate organoids.

A separate study by Lee et al. used our HPrEC cells to study the role of the androgen receptor (AR) in the proliferation of normal prostate cells. The AR is typically expressed in luminal epithelial cells and expressed at very low levels in basal epithelial cells. The authors characterized HPrECs and as expected, they found low levels of AR expression. Furthermore, inducing AR expression in HPrECs suppressed their proliferation but also promoted their differentiation into luminal epithelial cells. They concluded that the AR has a suppressive role in basal epithelial cell proliferation and a positive role in their differentiation. This study is important because it emphasizes the need for balancing AR expression in the prostate epithelium to maintain an appropriate balance between intermediate progenitor cells and differentiated luminal epithelial cells.

These two studies were made possible by products from Lifeline Cell Technology®:

• Lifeline® normal human prostate epithelial cells are derived from young healthy prostate tissue from donors who are all under the age of 30.
• These cells achieve maximum proliferation potential (up to 15 population doublings) in our newly developed ProstaLife™ prostate epithelial cell culture medium. ProstaLife™ is a serum-free medium that doesn’t contain antimicrobials or phenol red, both of which can cause cell stress and influence experimental results. For your convenience, ProstaLife™ can be ordered as a kit (ProstaLife™ Medium Complete Kit), which includes the basal medium, supplements, and growth factors and gives you the added benefit of formulation flexibility tailored to your experiments.

Have you used Lifeline Cell Technology® products to study prostate development and prostate cancer? Share your experience and findings with us!

References:

• Zhang et al. Role of CEACAM1 and CEACAM20 in an In Vitro Model of Prostate Morphogenesis. PLoS One. 2013;8(1):e53359.
• Lee et al. Suppressor role of androgen receptor in proliferation of prostate basal epithelial and progenitor cells. J Endocrinol. 2012;213(2):173-182.