Insulin-like growth factor binding protein-3 (IGFBP-3) in the prostate and in prostate cancer: local production, distribution and secretion pattern indicate a role in stromal-epithelial interaction.
BACKGROUND
Insulin-like growth factor binding protein 3 (IGFBP-3) exerts inhibitory and proapoptotic effects on prostate cancer cells. Serum levels of IGFBP-3 were found to be associated with the risk of prostate cancer, but the data are still inconclusive. We present a detailed analysis of the expression and localization of IGFBP-3 in the prostate and a comparison with its expression pattern in tumors.


METHODS
Expression and localization of IGFBP-3 were analyzed in cellular models and tissue by real-time RT-PCR, ELISA, immunohistochemistry, and immunofluorescence.


RESULTS
All cell types of a panel of benign epithelial, stromal and tumor prostate cells expressed IGFBP-3. Significantly higher expression levels were registered in stromal cells. TGF-beta stimulation boosted IGFBP-3 levels 60-fold in stromal cells. The pattern of expression was confirmed in microdissected tissue samples. Protein levels measured by ELISA paralleled the mRNA levels and more than 80% of IGFBP-3 was secreted. On tissue immunostaining, IGFBP-3 was found to be mainly located in the epithelium. The pattern suggested secretion of IGFBP-3, which was confirmed in prostate tissue cultured ex vivo and the ejaculate of vasectomized men. IGFBP-3 levels were increased in primary tumors but did not differ from benign epithelium in metastases and local recurrent tumors.


CONCLUSIONS
We registered a significant local production of IGFBP-3 in the prostate, which may well override the effect of protein entering from blood. The stroma--particularly reactivated stroma--is the main source of IGFBP-3 in the prostate, suggesting that this peptide acts as a mediator of stromal-epithelial interactions.
Massoner
Petra
P
Department of Urology, Innsbruck Medical University, Innsbruck, Austria.
Haag
Petra
P
Seifarth
Christof
C
Jurgeit
Andreas
A
Rogatsch
Hermann
H
Doppler
Wolfgang
W
Bartsch
Georg
G
Klocker
Helmut
H
D002450:Cell Communication / Q000502:physiology; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D004847:Epithelial Cells / Q000166:cytology*; D005455:Fluorescent Antibody Technique; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D032389:Myocytes, Smooth Muscle / Q000166:cytology; D011467:Prostate / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017154:Stromal Cells / Q000166:cytology* / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
C515497:IGFBP3 protein, human; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins; D016212:Transforming Growth Factor beta