Role of stromal tenascin-C in mouse prostatic development and epithelial cell differentiation
Role of stromal tenascin-C in mouse prostatic development and epithelial cell differentiation
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DOI：
10.1016/j.ydbio.2008.09.029
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发表时间：
2008-12-15
影响因子：
2.7
通讯作者：
Sugimura, Yoshiki
中科院分区：
文献类型：
--
作者：
Ishii, Kenichiro;Imanaka-Yoshida, Kyoto;Sugimura, Yoshiki
上皮-基质相互作用的失调被认为在良性前列腺增生（BPH）和前列腺癌（PCa）的发生和发展中起着关键作用。据报道，与正常前列腺相比，在BPH和PCa中，细胞外基质（ECM）糖蛋白生肿蛋白-C（TNC）的表达更高。ECM的重塑改变了上皮和基质之间的稳态平衡，导致细胞功能的生理变化。为了研究TN-C在前列腺发育和分化中的作用，我们评估了TN-C敲除（KO）小鼠前列腺（腹侧：VP，背外侧：DLP和前：AP）的形态表型，并检查了由成年小鼠DLP上皮和胎儿TN-C KO尿生殖窦间充质（UGM）组成的组织重组体。组织学分析显示TN-C KO AP和DLP中的上皮细胞簇突出到导管腔中。有趣的是，在8周时，在TN-C KO DLP的上皮中出现双核细胞。同时，雄激素受体（AR）阳性细胞减少TN-C KO上皮。与TN-C KO表型相似，通过与TN-C KO UGM重组，在DLP上皮中诱导了突出的上皮簇、双核细胞和AR阴性细胞核。我们的研究结果表明，基质TN-C可能参与维持上皮细胞分化，形态发生，雄激素受体表达正常的成年小鼠前列腺。(C)2008年爱思唯尔公司版权所有
Deregulation of epithelial-stromal interactions is considered to play a critical role in the initiation and promotion of benign prostatic hyperplasia (BPH) and prostate carcinoma (PCa). Expression of tenascin-C (TNC), an extracellular matrix (ECM) glycoprotein, is reportedly higher in BPH and PCa as compared with normal prostate. Remodeling of the ECM alters the homeostatic balance between epithelium and stroma, resulting in physiological changes in cellular functions. To investigate the role of TN-C in prostatic development and differentiation, we evaluated the morphological phenotype of TN-C knockout (KO) mouse prostate (ventral: VP, dorsolateral: DLP, and anterior: AP) and examined tissue recombinants composed of adult mouse DLP epithelium and fetal TN-C KO urogenital sinus mesenchyme (UGM). Histological analysis showed epithelial cell clusters protruding into the ductal lumens in TN-C KO AP and DLP. Interestingly, binucleated cells appeared in epithelium of TN-C KO DLP at 8 weeks. Simultaneously, androgen receptor (AR)-positive cells were decreased in TN-C KO epithelia. Similar to the TN-C KO phenotype, Protruded epithelial clusters, binucleated cells, and AR-negative nuclei were induced in DLP epithelium by recombining with TN-C KO UGM. Our results suggest that stromal TN-C might be involved in maintaining epithelial cytodifferentiation, morphogenesis, and androgen receptor expression of normal prostate glands in adult mice. (C) 2008 Elsevier Inc. All rights reserved