Understanding a little about the prostate gland and its biology is not only interesting, but it allows us to ask some important questions that can be very specific to our prostate cancer treatment decisions and our eventual outcomes from these decisions. It also can simply add to the confusion we all face in making the best clinical decisions.
Like other organs in the human body the prostate is composed of many different types of cells as well as extracellular components. During prostate development, cellular interactions between the stromal cells and the prostate epithelial cells will ultimately lead to the development of a mature prostate gland. The normal prostate gland is composed of a series of repeating cellular units that contain both stromal and epithelial compartments. The epithelial compartment contains luminal epithelial cells, basal cells and a minor component of neuroendocrine cells. Their function is believed to be to regulate the growth, differentiation and secretory function of the prostate gland.
We also know that neuroendocrine cells are present in prostate cancer. Numerous studies showed that the number of neuroendocrine increases in high grade and high stage tumors. This is especially true in hormonally treated and hormone-refractory (androgen-independent) prostate cancer.
Hormone therapy (ADT) reduces the secretion of the androgens from the prostate stromal cells that are critical for the survival for prostate epithelial cells. There is also evidence that the androgen receptor is also required for the tumorigenesis of human prostate cancer, so androgen deprivation therapy (ADT) likely works through the inhibition of the androgen receptor in the prostate epithelium. The catch is that neuroendocrine cells lack the androgen receptor and so are likely to be androgen-independent, it is conceivable that hormonal therapy for advanced/metastatic prostate cancer, which consists of inhibiting androgen production and/or blocking androgen receptor function, will not effect the neuroendocrine cancer cells. The paradox is that these neuroendocrine cells may become enriched after ADT and they may establish paracrine networks to stimulate androgen-independent proliferation of prostate cancer, leading to tumor recurrence and continued growth.
Am J Transl Res. 2009; 1(2): 148–162.
Published online 2009 Feb 5.
Neuroendocrine differentiation in prostate cancer