The role of stroma in prostatic carcinogenesis

Most human prostate tumors are adenocarcinomas which arise from the epithel ial cells that line the glands and ducts of the prostate. Consequently, the malignant epithelial cell, or more specifically genetic damage suffered by that malignant epithelial cell, has been the major focus of prostate cance r research to date. There is, however, increasing evidence to suggest that alterations in the stromal microenvironment associated with a malignant epi thelium may be necessary for progression of carcinogenesis. We have recently hypothesized that interactions between the stroma and epit helium become altered as a result of genetic damage to the prostatic epithe lial cell. During prostatic carcinogenesis, this abnormal signaling may lea d to changes in both the prostatic epithelium and smooth muscle with concom itant loss of growth control. In this way both a malignant epithelium and a n abnormal or 'tumor stroma' evolve. The purpose of this article is to describe interactions between the stroma and epithelium of the normal prostate, and then to summarize evidence sugge sting that stromal cells derived from benign versus malignant sources may e xert differential effects on epithelial cell growth and differentiation.