Massoner Petra, Haag Petra, Seifarth Christof, Jurgeit Andreas, Rogatsch Hermann, Doppler Wolfgang, Bartsch Georg, Klocker Helmut
Department of Urology, Innsbruck Medical University, Innsbruck, Austria.
Prostate. 2008 Aug 1;68(11):1165-78. doi: 10.1002/pros.20785.
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.
Expression and localization of IGFBP-3 were analyzed in cellular models and tissue by real-time RT-PCR, ELISA, immunohistochemistry, and immunofluorescence.
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.
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.
胰岛素样生长因子结合蛋白3（IGFBP - 3）对前列腺癌细胞具有抑制和促凋亡作用。血清IGFBP - 3水平与前列腺癌风险相关，但数据仍无定论。我们对IGFBP - 3在前列腺中的表达和定位进行了详细分析，并与它在肿瘤中的表达模式进行了比较。
通过实时逆转录聚合酶链反应、酶联免疫吸附测定、免疫组织化学和免疫荧光分析IGFBP - 3在细胞模型和组织中的表达及定位。
一组良性上皮、基质和肿瘤前列腺细胞的所有细胞类型均表达IGFBP - 3。基质细胞中的表达水平显著更高。转化生长因子β刺激使基质细胞中的IGFBP - 3水平提高了60倍。在显微切割的组织样本中证实了这种表达模式。酶联免疫吸附测定法测得的蛋白质水平与mRNA水平平行，且超过80%的IGFBP - 3被分泌。在组织免疫染色中，发现IGFBP - 3主要位于上皮中。这种模式提示了IGFBP - 3的分泌，这在体外培养的前列腺组织和输精管结扎男性的精液中得到了证实。原发性肿瘤中IGFBP - 3水平升高，但在转移瘤和局部复发肿瘤中与良性上皮无差异。
我们发现前列腺中存在显著的IGFBP - 3局部产生，这很可能会超过从血液进入的蛋白质的作用。基质——尤其是重新激活的基质——是前列腺中IGFBP - 3的主要来源，表明该肽作为基质 - 上皮相互作用的介质发挥作用。
