研究表明，炎症与高级侵袭性前列腺肿瘤的发展以及最终的转移有着协同作用，在过去的几年中已经进行了大量的工作。然而，炎症引发前列腺癌的明确机制仍然大部分未被描述。我们先前的研究已经表明，条件培养基(CM)介导的LNCaP细胞迁移与抑癌基因NKX3.1的表达丧失部分相关。在这里，我们继续研究炎症介导的前列腺癌细胞迁移以及NKX3.1在这个过程中的作用，以全面了解细胞迁移相关变化。此前，我们的研究小组已经优化了肿瘤微环境中的炎症模型；在这里，我们继续研究CM暴露的时间依赖效应以及NKX3.1的变化，我们观察到这些变化在获得异质上皮-间质转变(EMT)表型方面发挥着重要作用。因此，这是肿瘤进展的一个重要参数；我们使用CRISPR/Cas9系统降低了NKX3.1的表达，并检查了在暴露于炎症细胞因子后迁移的细胞群。我们发现迁移的细胞明显表现出可逆的E-cadherin表达丧失，与对照细胞相比，这与随后的vimentin表达改变一致。此外，数据表明AR介导的转录程序对前列腺癌进展中的间质-上皮转变(MET)也起到贡献作用。此外，定量蛋白质组学分析显示，来自同一细胞系的迁移亚群呈现出不同的表型，过表达的蛋白质参与了细胞代谢和RNA加工。根据KEGG通路分析，ABC转运体被发现是最显著的。因此，细胞迁移的动态过程有利于在不断变化的肿瘤微环境中获得多样的基因组成。不同水平的侵袭性通过在这些EMT和MET表型之间转变细胞来支持。© 2023 作者。美国化学学会发表。

Studies demonstrate that inflammation synergizes with high-grade aggressive prostate tumor development and ultimately metastatic spread, in which a lot of work has been done in recent years. However, the clear mechanism of inflammation inciting prostate cancer remains largely uncharacterized. Our previous study has shown that the conditioned media (CM)-mediated LNCaP cell migration is partially correlated with the loss of expression of the tumor suppressor NKX3.1. Here, we continue to investigate the inflammation-mediated migration of prostate cancer cells, and the role of NKX3.1 in this process to gain insights into cell migration-related changes comprehensively. Earlier, the model of inflammation in the tumor microenvironment have been optimized by our research group; here, we continue to investigate the time-dependent effect of CM exposure together with NKX3.1 changes, in which we observed that these changes play important roles in gaining heterogeneous epithelial-to-mesenchymal transition (EMT) phenotype. Hence, this is an important parameter of tumor progression; we depleted NKX3.1 expression using the CRISPR/Cas9 system and examined the migrating cell clusters after exposure to inflammatory cytokines. We found that the migrated cells clearly demonstrate reversible loss of E-cadherin expression, which is consistent with subsequent vimentin expression alterations in comparison to control cells. Moreover, the data suggest that the AR-mediated transcriptional program also contributes to mesenchymal-to-epithelial transition (MET) in prostate cancer progression. Furthermore, the quantitative proteomic analysis showed that migrated subpopulations from the same cell line presented different phenotypes in which the proteins overexpressed are involved in cell metabolism and RNA processing. According to KEGG pathway analysis, the ABC transporters were found to be the most significant. Thus, the dynamic process of cellular migration favors diverse genetic compositions under changing tumor microenvironments. The different levels of invasiveness are supported by shifting the cells in between these EMT and MET phenotypes.© 2023 The Authors. Published by American Chemical Society.