Prostate cancer (PCa) is one of the most common cancers in men. Metastasis is the leading cause of death in prostate cancer patients. One of the crucial processes involved in metastatic spread is the “epithelial–mesenchymal transition” (EMT), which allows cells to acquire the ability to invade distant organs. Liver X Receptors (LXRs) are nuclear receptors that have been demonstrated to regulate EMT in various cancers, including hepatic cancer. Our study reveals that the LXR pathway can control pro-invasive cell capacities through EMT in prostate cancer, employing ex vivo and in vivo approaches. We characterized the EMT status of the commonly used LNCaP, DU145, and PC3 prostate cancer cell lines through molecular and immunohistochemistry experiments. The impact of LXR activation on EMT function was also assessed by analyzing the migration and invasion of these cell lines in the absence or presence of an LXR agonist. Using in vivo experiments involving NSG-immunodeficient mice xenografted with PC3-GFP cells, we were able to study metastatic spread and the effect of LXRs on this process. LXR activation led to an increase in the accumulation of Vimentin and Amphiregulin in PC3. Furthermore, the migration of PC3 cells significantly increased in the presence of the LXR agonist, correlating with an upregulation of EMT. Interestingly, LXR activation significantly increased metastatic spread in an NSG mouse model. Overall, this work identifies a promoting effect of LXRs on EMT in the PC3 model of advanced prostate cancer.
前列腺癌是男性最常见的癌症之一。转移是前列腺癌患者死亡的主要原因。转移扩散过程中的关键环节之一是"上皮-间质转化"，这一过程使细胞获得侵袭远处器官的能力。肝X受体作为核受体，已被证实在包括肝癌在内的多种癌症中能够调控上皮-间质转化。本研究通过离体和在体实验方法揭示，在前列腺癌中LXR通路可通过上皮-间质转化调控细胞的促侵袭能力。我们通过分子生物学和免疫组化实验，对常用的LNCaP、DU145和PC3前列腺癌细胞系的上皮-间质转化状态进行了表征。通过分析这些细胞系在LXR激动剂存在或缺失条件下的迁移和侵袭能力，评估了LXR激活对上皮-间质转化功能的影响。利用植入PC3-GFP细胞的NSG免疫缺陷小鼠进行在体实验，我们成功研究了转移扩散过程及LXR对该过程的影响。LXR激活导致PC3细胞中波形蛋白和双调蛋白的积累增加。此外，在LXR激动剂存在下，PC3细胞的迁移能力显著增强，这与上皮-间质转化的上调相关。值得注意的是，在NSG小鼠模型中，LXR激活显著增加了转移扩散。总体而言，本研究在晚期前列腺癌PC3模型中确定了LXR对上皮-间质转化的促进作用。
Liver X Receptors Enhance Epithelial to Mesenchymal Transition in Metastatic Prostate Cancer Cells
肿瘤(癌症)患者之家