The role of stroma in prostatic carcinogenesis

Abstract

Abstract Most human prostate tumors are adenocarcinomas which arise from the epithelial 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 cancer research to date. There is, however, increasing evidence to suggest that alterations in the stromal microenvironment associated with a malignant epithelium may be necessary for progression of carcinogenesis. We have recently hypothesized that interactions between the stroma and epithelium become altered as a result of genetic damage to the prostatic epithelial cell. During prostatic carcinogenesis, this abnormal signaling may lead to changes in both the prostatic epithelium and smooth muscle with concomitant loss of growth control. In this way, both a malignant epithelium and an 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 suggesting that stromal cells derived from benign versus malignant sources may exert differential effects on epithelial cell growth and differentiation. Acknowledgements This work was supported by NIH grants DK52721, CA 59831, DK 45861, CA 64872, DK 52708 and DK 47517, and by an AFUD/Pfizer USPG Research Scholarship to GDG.