Prostate Cancer and the Search for New Biomarkers

The prostate is part of the male reproductive system, responsible for making and secreting part of the seminal fluid, which supports the health and survival of semen. The secretory cells of the prostate are the prostate epithelial cells, which are also the cell type of origin from which prostate cancer develops. Prostate cancer is the second leading cause of cancer-related death in men, and is estimated to kill just over 29,000 men this year. Many men will have a PSA test during their yearly physical, which measures the levels of prostate-specific antigen (PSA) in the blood. Although the reliability of this test is debated, high levels of PSA can indicate the presence of prostate cancer, which makes PSA a biological marker, or biomarker.

When faced with a cancer diagnosis, the first thing we want to know are the odds. The odds of survival or the odds that a certain treatment will or won’t work. These types of odds are often informed by biomarkers, which are biological characteristics of a disease. For example, PSA might indicate that an individual has prostate cancer. Or, the status of expression of the androgen receptor and its splice variants in a prostate tumor might indicate whether that tumor is likely to be castration-resistant, or have a poor prognosis.

To determine whether a biological characteristic is associated with any clinical outcomes, researchers will examine its correlation with certain aspects of a disease. In prostate cancer, for instance, one might evaluate correlation with tumor risk (tumor severity), Gleason score (tumor aggressiveness), D’Amico risk (5-year risk of treatment failure), or International Society of Urological Pathology (ISUP) grade (tumor grade classification). Biomarkers are important factors that help define individual tumors and continual identification of new biomarkers is important for understanding cancer and informing treatment.

NEW Lifeline® Prostate Cells!

Lifeline® is announcing the addition of NEW prostate smooth muscle cells and prostate fibroblasts, optimized for growth in VascuLife® and FibroLife® medium, respectively. In addition to the epithelium, described above, the prostate contains fibroblasts and smooth muscle cells that are contained in the stroma surrounding the epithelium. In combination with our prostate epithelial cells these cells provide ideal models with which to study prostate biology.

Recent Research Using Lifeline® Normal Human Prostate Epithelial Cells

Aquaporins (AQPs) are transmembrane proteins through which uncharged molecules, like water, pass. AQPs have been implicated in various diseases, including cancer, although they have not been systematically characterized in the prostate. In a 2018 study in BMC Urology, Bründle and colleagues set out to determine whether there is potential clinical significance associated with expression of any of the 13 AQPs. First, using Lifeline® normal human prostate epithelial cells, along with prostate cancer cell lines (LNCaP, DU-145, and PC3), the researchers detected transcript expression of AQP 1, 3, 4, 7, 8, 10, and 11 in all cell types examined. AQP 5 mRNA was detected in only DU-145 and PC3 cells, AQP 6 mRNA was detected in all but LNCaP cells, and AQP 9 mRNA was detected only in normal Lifeline® prostate epithelial cells. These results were confirmed by immunofluorescence.

To further determine whether the expression of AQPs has any clinical significance, the authors performed immunohistochemistry and qPCR to evaluate AQP protein and transcript expression, respectively, in benign and malignant prostate tissue from human patients. AQP 3, 5, 7, and 9 were expressed in benign human prostate tissue, although AQP3 was the most highly expressed. Interestingly, in prostate cancer tissue samples, AQP3 expression was varied, but compared with tumors of lower malignancy, AQP 3 protein expression was lower in more malignant tumors and absent from one-third of high-risk tumors.

Additionally, AQP 9 expression was was absent from malignant prostate tissue. When the authors examined whether the mRNA expression of AQPs correlated with the observed protein expression, they found that AQP 3 mRNA was correlated with PSA levels, D’Amico risk stratification, ISUP grade, and Gleason score. AQP 4 transcript expression was correlated with the presence of a tumor, D’Amico risk stratification, ISUP grade, and Gleason score. Finally, AQP 9 mRNA expression was negatively correlated with PSA.

Together, the results of this study illustrate some interesting correlations between AQP expression and prostate cancer. Further studies with larger cohorts and normal human prostate tissue samples will confirm whether these observations translate to the larger population.

How are you using Lifeline® cells to answer your scientific questions? Let us know and your study could be featured here on the blog!

Statistics from www.cancer.org.