The role of stromal cells in prostate cancer development and progression

Prostate cancer is one of the most common malignancies in males, and tumor progression critically determines its clinical significance. Prostatic stromal cells may be critically involved in growth and progression of prostate cancer. There is substantial evidence that the stromal component of the embryological tissue of origin, the urogenital sinus, is essential in directing outgrowth and prostatic differentiation of the epithelial anlage of the prostate. The presence of a stromal androgen receptor is required for this effect, and humoral factors, such as keratinocyte growth factor, have been shown to be able to mediate it in a paracrine fashion. The adult prostate is also under control of multiple steroid hormone and paracrine peptide factors, and there is evidence that the prostatic stroma plays a major role in mediation of androgen effects on prostatic epithelium. Normal seminal vesicle mesenchyme can cause differentiation of the Dunning R3327H prostate carcinoma. Normal rat prostatic fibroblasts influence the in vivo and soft agar growth of epithelial cells derived from chemically/hormonally induced rat prostate carcinomas, as do fibroblasts that are isolated from these tumors. Both growth-enhancing and growth-inhibiting effects were observed, apparently depending on the stage of progression of both cell types as well as on whether fibroblasts were derived from the same or a different tumor than the epithelial cells. These findings indicate that stromal cells critically influence epithelial prostate cancer growth, and they suggest that these effects can significantly vary in different tumors as well as in different stages of tumor progression.