Pancreatic ductal adenocarcinoma (PDAC) is mostly diagnosed at advanced or even metastasized stages, limiting the prognoses of patients. Metastasis requires high tumor cell plasticity, implying phenotypic switching in response to changing environments. Here, epithelial–mesenchymal transition (EMT), being associated with an increase in cancer stem cell (CSC) properties, and its reversion are important. Since it is poorly understood whether different CSC phenotypes exist along the EMT axis and how these impact malignancy-associated properties, we aimed to characterize CSC populations of epithelial and mesenchymal-like PDAC cells. Single-cell cloning revealed CSC (Holoclone) and non-CSC (Paraclone) clones from the PDAC cell lines Panc1 and Panc89. The Panc1 Holoclone cells showed a mesenchymal-like phenotype, dominated by a high expression of the stemness marker Nestin, while the Panc89 Holoclone cells exhibited a SOX2-dominated epithelial phenotype. The Panc89 Holoclone cells showed enhanced cell growth and a self-renewal capacity but slow cluster-like invasion. Contrarily, the Panc1 Holoclone cells showed slower cell growth and self-renewal ability but were highly invasive. Moreover, cell variants differentially responded to chemotherapy. In vivo, the Panc1 and Panc89 cell variants significantly differed regarding the number and size of metastases, as well as organ manifestation, leading to different survival outcomes. Overall, these data support the existence of different CSC phenotypes along the EMT axis in PDAC, manifesting different metastatic propensities.
胰腺导管腺癌（PDAC）大多在晚期甚至转移阶段才被诊断，限制了患者的预后。转移需要肿瘤细胞具有高度可塑性，这意味着表型会随环境变化而转换。其中，上皮-间质转化（EMT）及其逆转过程至关重要，该过程与癌症干细胞（CSC）特性的增强相关。由于目前对EMT轴线上是否存在不同的CSC表型及其如何影响恶性特征尚不清楚，本研究旨在表征上皮型和间质样PDAC细胞中的CSC群体。通过单细胞克隆技术，从PDAC细胞系Panc1和Panc89中分离出CSC（全克隆）和非CSC（旁克隆）克隆。Panc1全克隆细胞呈现间质样表型，以高表达干性标志物巢蛋白为特征；而Panc89全克隆细胞则表现出以SOX2为主导的上皮表型。Panc89全克隆细胞表现出增强的细胞增殖和自我更新能力，但呈缓慢的簇状侵袭模式。相反，Panc1全克隆细胞增殖和自我更新能力较弱，却具有高侵袭性。此外，不同细胞变体对化疗的反应存在差异。在体内实验中，Panc1和Panc89细胞变体在转移灶数量与大小、器官转移分布方面差异显著，导致不同的生存结局。总体而言，这些数据支持PDAC中沿EMT轴线存在不同CSC表型的观点，这些表型表现出不同的转移倾向。
肿瘤(癌症)患者之家