Reprogramming of Prostate Stromal Cells by Prostate Inflammation

 描述（由申请人提供）：基底细胞和腔细胞是前列腺中两种主要类型的上皮细胞。这两种类型的细胞在成年人中大多独立存在，两者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管腔细胞的前列腺癌更具侵袭性。有趣的是，这种侵袭性类型的前列腺癌的发生受到称为基底细胞向管腔细胞分化的细胞过程的限制。我们最近发现，在前列腺炎诱导的背景下，基底细胞到管腔的分化增强， 来自尿路病原菌感染，表明前列腺基质微环境实质上影响前列腺基底上皮细胞的分化程序。在本申请中，我们建议使用分子生物学和遗传学方法的组合来揭示细菌感染诱导的前列腺炎如何影响前列腺基质细胞转录组。我们试图确定前列腺基质细胞介导的信号传导，在调节基底上皮细胞分化中发挥关键作用，并验证它们是否作为侵袭性前列腺癌的预后标志物。

 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.