Preprostatectomy: A clinical model to study stromal-epithelial interactions

Citation
W. Lopacznski et al., Preprostatectomy: A clinical model to study stromal-epithelial interactions, UROLOGY, 57(4A), 2001, pp. 194-199
Citations number
42
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Urology & Nephrology
Journal title
UROLOGY
ISSN journal
0090-4295 → ACNP
Volume
57
Issue
4A
Year of publication
2001
Supplement
S
Pages
194 - 199
Database
ISI
SICI code
0090-4295(200104)57:4A<194:PACMTS>2.0.ZU;2-0
Abstract
The preprostatectomy setting serves as a valuable clinical model for early developmental clinical trials for evaluating promising agents for chemoprev ention. In the preprostatectomy model, study agents are administered betwee n the diagnostic biopsy for prostate cancer and definitive therapy. The pro static tissue that is available after prostatectomy allows for biomarker ev aluation of all the components of the prostate, including the glandular epi thelium, blood vessels, and the stroma. This provides an opportunity to stu dy the reciprocal interactions between the stroma and the epithelium. Morph ologic studies suggest that prostatic stromal cells play a critical role in affecting the growth and maturation of prostatic epithelium. Experimental studies in tissue culture show that carcinoma-associated stromal cells can promote prostatic carcinogenesis, and normal stromal cells may be able to i nhibit prostatic carcinogenesis by inducing differentiation and decreasing the proliferation of the epithelium. Although the complex molecular mechani sms through which stroma modulates the epithelial cell phenotype remain to be elucidated, there are several well-characterized signaling pathways, suc h as for growth factors and steroid hormones, that are likely to contribute to the modulation of transformed epithelial cells. There is evidence of an association between increased serum levels of ICF-I and an increased risk of prostate cancer. The IGF system appears to play an important role in the development of prostate cancer by modulation of paracrine pathways, and al so by modulation of the concentrations of different stromal and epithelial IGFBP, which are differentially expressed in the epithelium and stroma. Ner ve growth factor is capable of stimulating a proliferative response via a h igh affinity Trk receptor present in normal and malignant prostate epitheli a, and alternatively can mediate apoptosis via the low affinity p75NTR rece ptor that is progressively lost from the malignant prostate. As the role of each stromal element involved in carcinogenesis becomes further defined, t hese elements offer promising targets for new chemopreventive strategies.