Prostate development and pathogenesis.
Prostate development and pathogenesis.
复制标题
前列腺发育和发病机制。
DOI：
10.1111/j.1432-0436.2008.00303.x
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发表时间：
2008
期刊：
影响因子：
--
通讯作者：
Marker,PaulC
中科院分区：
文献类型：
--
作者：
Thomson,AxelA;Cunha,GeraldR;Marker,PaulC
Journal compilation r 2008, International Society of Differentiation pathologist interested in BPH and prostatic cancer. He recognized that the neo-formation of ductal-acinar architecture in aging men during the pathogenesis of BPH resembled the process of prostatic development in the embryo. Accordingly, McNeal proposed the idea that the neo-formation of ductal-acinar architecture in the pathogenesis of BPH was due to the reactivation of embryonic inductivity in adult prostatic stroma. If this idea is true, then the BPH stroma must acquire (or have retained) embryonic-like inductivity, and adult prostatic epithelium must also acquire (or have retained) responsiveness to embryonic induction. For technical reasons, the ability of adult prostatic stroma to induce the neoformation of branched ductal networks has not been established adequately and remains a challenging problem. Regarding responsiveness of the adult epithelium to embryonic induction, a series of studies from the Cunha lab have established the following: adult epithelial differentiation and function are dependent on continued stromal–epithelial interactions in which stromal cells maintain the epithelium in a growth-quiescent highly differentiated state (Cunha et al., 1985). Bringing fully differentiated growth-quiescent adult prostatic epithelium (or bladder epithelium) into contact with embryonic prostatic mesenchyme can completely reprogram adult epithelial differentiation, presumably due to transdifferentiation of adult epithelial cells or differentiation of adult multipotent stems cells resident in the epithelia of the adult urogenital tract (see review by Taylor and Risbridger, this issue). Finally, studies from the Cunha lab established the idea that mesenchymal–epithelial interactions are reciprocal in nature. While the mesenchyme induces epithelial differentiation, the developing prostatic epithelium in turn induces mesenchymal differentiation. For organs of the urogenital system such as the prostate, this means that differentiation of the mesenchyme into smooth muscle is dependent on the paracrine action of the normal epithelium on the mesenchyme. From the studies pioneered by Simon Hayward, we have arrived at a unifying concept of normal development, adult homeostasis, and malignant progression. The model involves the following events: the urogenital sinus mesenchyme induces the urogenital sinus epithelium to undergo prostatic ductal morphogenesis and differentiation. During prostatic epithelial differentiation, the epithelium signals the urogenital sinus mesenchyme to differentiate into smooth muscle cells that surround the epithelial ducts. Thus, differentiation of prostatic smooth muscle requires both androgens and an inductive signal from the epithelium. Once formed, the prostatic smooth muscle participates in reciprocal homeostatic interactions in which it maintains epithelial differentiation under the influence of androgens. In turn, the prostatic epithelium signals the maintenance of smooth muscle differentiation. Such reciprocal homeostatic interactions during adulthood maintain a highly differentiated state and growth quiescence in both cell types. The process of prostatic carcinogenesis, presumably initiated following genetic damage to the prostatic epithelium, is proposed to involve progressive disruption of these reciprocal homeostatic interactions, with the resultant de-differentiation of both the emerging prostatic carcinoma cells and the smooth muscle. As smooth muscle differentiation begins to drift, signaling from the prostatic smooth muscle to the epithelium becomes abnormal resulting in loss of control over epithelial differentiation and proliferation, thus establishing a vicious cycle …
