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
| Autor: | Georg Bartsch, Hermann Rogatsch, Petra Haag, Helmut Klocker, Petra Massoner, Wolfgang Doppler, Christof Seifarth, Andreas Jurgeit |
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| Rok vydání: | 2008 |
| Předmět: |
PCA3
Male medicine.medical_specialty Stromal cell Urology Myocytes Smooth Muscle Fluorescent Antibody Technique Cell Communication Biology Insulin-like growth factor-binding protein Prostate cancer Prostate Transforming Growth Factor beta Internal medicine Cell Line Tumor medicine Humans Cell Line Transformed Reverse Transcriptase Polymerase Chain Reaction Cancer Prostatic Neoplasms Epithelial Cells medicine.disease Epithelium Coculture Techniques Up-Regulation Gene Expression Regulation Neoplastic Insulin-Like Growth Factor Binding Proteins Endocrinology medicine.anatomical_structure Insulin-Like Growth Factor Binding Protein 3 Oncology Cancer research biology.protein Immunohistochemistry Stromal Cells |
| Zdroj: | The Prostate. 68(11) |
| ISSN: | 0270-4137 |
| Popis: | 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-β 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. Prostate 68: 1165–1178, 2008. © 2008 Wiley-Liss, Inc. |
| Databáze: | OpenAIRE |
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