Reprogramming of Prostate Stromal Cells by Prostate Inflammation

 描述(申请人提供)：基细胞和腔细胞是前列腺中两种主要的上皮细胞类型。这两种类型的细胞大多在成人中独立存在，都可以作为前列腺癌的起源细胞。最近使用小鼠模型的研究表明，起源于基底上皮细胞的前列腺癌比起源于腔上皮细胞的前列腺癌更具侵袭性。有趣的是，这种浸润性前列腺癌的发生受到称为基底腔分化的细胞过程的限制。我们最近发现，在前列腺炎的情况下，基底到腔的分化是增强的。 来自泌尿系病原菌的感染，提示前列腺间质微环境对前列腺基底上皮细胞的分化程序有实质性的影响。在这一应用中，我们建议使用分子生物学和遗传学方法相结合的方法来揭示细菌感染导致的前列腺炎如何影响前列腺基质细胞转录组。我们试图确定在调节基底上皮细胞分化中起关键作用的前列腺基质细胞介导的信号，并验证它们是否可以作为侵袭性前列腺癌的预后标志。

 DESCRIPTION (provided by applicant): Basal and luminal cells are the two major types of epithelial cells in the prostate. These two types of cells are mostly independently sustained in adults and both can serve as the cells of origin for prostate cancer. Recent studies using mouse models revealed that prostate cancer originated from basal epithelial cells are more invasive than those derived from luminal cells. Interestingly, initiation of this invasive type of prostate cancer is limited by a cellular process called basal-to-luminal differentiation. We showed recently that basal-to-luminal differentiation is enhanced in the context of prostatitis induced by infection from uropathogenic bacteria, suggesting that prostate stromal microenvironment substantially impinge on the differentiation program of prostate basal epithelial cells. In this application, we propose to use a combination of molecular biological and genetic approaches to uncover how the bacterial infection induced prostatitis affects prostate stromal cell transcriptome. We seek to identify prostate stromal cell-mediated signaling that plays critical roles in regulation of basal epithelial cell differentiation, and verify whether they serve as prognostic markers for aggressive prostate cancer.