Negative control of epithelial cell proliferation by prostatic stroma

Prostatic diseases are rather frequently occurring disorders in the male population. Prostatic adenoma -better known as benign prostatic hyperplasia (BPH)- is the most common benign neoplasm in men. Prostate cancer is the most commonly diagnosed malignancy in men and second leading cause of male cancer death in 'Western countries!. In The Netherlands, the morbidity and mortality caused by this tumor are exceeded only by those originating in lung cancer; in 1991, 4,343 incident cases and 2,108 deaths from cancer of the prostate were recorded in a male population of 7.5 million. The risk of developing prostate cancer increases dramatically with age, as does the oCcurrence of the proliferative disorder BPH. Indeed, men over the age of 65 that do not present with symptoms of prostate cancer during life very frequently are found to contain microscopic malignant lesions upon autopsy. Many patients with prostatic cancer are diagnosed with disseminated disease. The majority of these disseminated prostatic carcinomas are androgen dependent and respond to hormonal manipulation, i.e. medical or surgical castration. The effectiveness of this therapy, however, is only temporary; after an initial response the tumor escapes from endocrine regulation to become insensitive to treatment based on the withdrawal or blockade of androgens. Such patients will eventually die of disseminated hormone-refractory prostate cancer. The etiology of prostate cancer is not clearly defined, it is thought to be multifactorial, involving genetic, hormonal, dietary and environmental causes. The mechanisms leading to progression of prostate tumors to autonomy are also largely unknown. Moreover, despite decades of experience with different treatment modalities, there are still controversies relating to patient selection criteria and choice of treatment. The recent development of different (medical) treatments for BPH has given rise to similar discussions concerning benign enlargement of the gland.

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