Cellular interactions in prostate cancer.
This article will review the different modes of action of soluble growth factors in the growth of benign and malignant prostatic cells. Cellular proliferation, growth arrest or even apoptosis requires the participation of appropriate growth factors [1]. Proliferative activities of prostatic epithelial cells, like other cells, are governed by the action of a variety of growth factors. Prostatic growth is traditionally considered to be regulated by androgen, as the prostate is an androgen-sensitive organ, in that the growth and maintenance of the structure and functional integrity are dependent upon the presence of circulating androgen [2,3]. A depletion of this androgenic support, e.g. by bilateral orchidectomy in the host, results in massive apoptosis in prostatic epithelial cells, leading to a rapid rate of tissue involution [4]. Subsequent androgen replacement therapy reactivates prostatic growth. Therefore, androgen is the most potent mitogen to the prostate. It is now apparent that this mitogenic effect of androgen on the prostate is mediated through the action of various growth factors as a consequence of an intricate cell-to-cell interaction, a characteristic feature of benign prostatic growth [5,6]. On the other hand, malignant prostatic growth is characterized by additional mechanisms of cellular proliferation that provide a distinct growth advantage over that of their benign counterparts. Cancer develops as a result of a series of genetic mutations [7]. Prostatic cancer is no exception; however, its progression seems to follow a relatively predictable course, from an androgen-sensitive state to an autonomous state [8]. Sensitivity to androgen in prostatic cancer is mainly due to the presence of androgen receptors in malignant cells, which retain some properties of the benign prostatic cells. However, the manner in which androgen interacts with prostatic cancer cells can be drastically different from that in which it reacts with benign cells. Despite androgen playing an important role in the progression of prostatic cancer, eventually these cancer cells are able to convert from an androgen-responsive growth mode to an androgen-independent mode. Often, a conversion from one state to another is associated with a poorer prognosis and is preceded by the acquisition of new growth advantages within the cancer cells. Again, soluble growth factors are the underlying mechanisms of androgen-sensitive and androgen-insensitive malignant growth. The abnormal growth behaviour in prostatic cancer cells can be manifested by an over-expression of growth-stimulating factor(s) and/or a loss of expression (or function) of growth-suppressive factor(s). The production and action of growth factors in the context of benign and malignant growth of prostatic cells will be the focus of the present discussion.
Lee
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Department of Urology, Northwestern University Medical School, Chicago, IL 60611, USA.
D000728:Androgens / Q000502:physiology*; D000818:Animals; D002450:Cell Communication / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D016207:Cytokines / Q000502:physiology; D016147:Genes, Tumor Suppressor; D006133:Growth Substances / Q000502:physiology*; D006801:Humans; D008297:Male; D051379:Mice; D009154:Mutation; D009857:Oncogenes / Q000502:physiology; D011471:Prostatic Neoplasms / Q000473:pathology*
D000728:Androgens; D016207:Cytokines; D006133:Growth Substances