Expression of Pleiotrophin in the Prostate Is Androgen Regulated and it Functions as an Autocrine Regulator of Mesenchyme and Cancer Associated Fibroblasts and as a Paracrine Regulator of Epithelia
Expression of Pleiotrophin in the Prostate Is Androgen Regulated and it Functions as an Autocrine Regulator of Mesenchyme and Cancer Associated Fibroblasts and as a Paracrine Regulator of Epithelia
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DOI：
10.1002/pros.21244
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发表时间：
2011-02-15
期刊：
影响因子：
2.8
通讯作者：
Thomson, Axel A.
中科院分区：
文献类型：
--
作者：
Orr, Brigid;Vanpoucke, Griet;Thomson, Axel A.
背景。来自间质/间质的雄激素和旁分泌信号调节前列腺的发育和疾病，诱导前列腺间质的基因谱研究已经确定了候选分子，如多营养蛋白（Ptn）。采用原位和免疫组织化学方法对Ptn转录本和蛋白进行定位，采用Northern blot和qRT-PCR对Ptn mRNA进行定量分析。通过在大鼠腹侧前列腺器官培养物、原代人胎前列腺成纤维细胞、前列腺癌相关成纤维细胞和BPH1上皮中添加hPTN蛋白来检测Ptn的功能。在发育过程中，Phi转录本和蛋白在腹侧间质垫（VIMP）和前列腺间质中表达。Ptn定位于导管上皮尖端周围的间质，发生分支形态形成，位于上皮表面。当将hPTN蛋白添加到大鼠VP培养物中时，可刺激分支形态发生、基质和上皮细胞增殖，并刺激胎儿人前列腺成纤维细胞、前列腺癌相关成纤维细胞和BPH1上皮细胞的生长。PTN mRNA在患者匹配的正常前列腺成纤维细胞与前列腺癌相关成纤维细胞中富集。PTN在胎儿人类雄性尿道中表达也比雌性高，在wt雄性和ARKO雄性小鼠中表达也比雌性高。在胎儿人前列腺成纤维细胞和雌性大鼠VMP器官培养中，PTN转录物被睾酮上调。雌性大鼠VMP和雄性大鼠尿道器官培养中Ptn蛋白比雌性大鼠增加。我们的数据表明，在前列腺中，Ptn作为间充质和上皮细胞增殖的调节剂，雄激素调节Ptn水平。中华医学会医学分会，2011。(C) 2010 Wiley-Liss, Inc。
BACKGROUND. Androgens and paracrine signaling from mesenchyme/stroma regulate development and disease of the prostate, and gene profiling studies of inductive prostate mesenchyme have identified candidate molecules such as pleiotrophin (Ptn).METHODS. Ptn transcripts and protein were localized by in situ and immunohistochemistry and Ptn mRNA was quantitated by Northern blot and qRT-PCR. Ptn function was examined by addition of hPTN protein to rat ventral prostate organ cultures, primary human fetal prostate fibroblasts, prostate cancer associated fibroblasts, and BPH1 epithelia.RESULTS. During development, Phi transcripts and protein were expressed in ventral mesenchymal pad (VIMP) and prostatic mesenchyme. Ptn was localized to mesenchyme surrounding ductal epithelial tips undergoing branching morphogenesis, and was located on the surface of epithelia. hPTN protein stimulated branching morphogenesis and stromal and epithelial proliferation, when added to rat VP cultures, and also stimulated growth of fetal human prostate fibroblasts, prostate cancer associated fibroblasts, and BPH1 epithelia. PTN mRNA was enriched in patient-matched normal prostate fibroblasts versus prostate cancer associated fibroblasts. PTN also showed male enriched expression in fetal human male urethra versus female, and between wt male and ARKO male mice. Transcripts for PTN were upregulated by testosterone in fetal human prostate fibroblasts and organ cultures of female rat VMP. Ptn protein was increased by testosterone in organ cultures of female rat VMP and in rat male urethra compared to female.CONCLUSIONS. Our data suggest that in the prostate Ptn functions as a regulator of both mesenchymal and epithelial proliferation, and that androgens regulate Ptn levels. Prostate 71: 305-317, 2011. (C) 2010 Wiley-Liss, Inc.