Endometrial cancer is one of the most common gynaecological malignancies. Although often diagnosed at an early stage, there is a subset of patients with recurrent and metastatic disease for whom current treatments are not effective. Cancer stem cells (CSCs) play a pivotal role in triggering tumorigenesis, disease progression, recurrence, and metastasis, as high aldehyde dehydrogenase (ALDH) activity is associated with invasiveness and chemotherapy resistance. Therefore, this study aimed to evaluate the effects of ALDH inhibition in endometrial CSCs. ECC-1 and RL95-2 cells were submitted to a sphere-forming protocol to obtain endometrial CSCs. ALDH inhibition was evaluated through ALDH activity and expression, sphere-forming capacity, self-renewal, projection area, and CD133, CD44, CD24, and P53 expression. A mass spectrometry-based proteomic study was performed to determine the proteomic profile of endometrial cancer cells upon N,N-diethylaminobenzaldehyde (DEAB). DEAB reduced ALDH activity and expression, along with a significant decrease in sphere-forming capacity and projection area, with increased CD133 expression. Additionally, DEAB modulated P53 expression. Endometrial cancer cells display a distinct proteomic profile upon DEAB, sharing 75 up-regulated and 30 down-regulated proteins. In conclusion, DEAB inhibits ALDH activity and expression, influencing endometrial CSC phenotype. Furthermore, ALDH18A1, SdhA, and UBAP2L should be explored as novel molecular targets for endometrial cancer.
子宫内膜癌是最常见的妇科恶性肿瘤之一。尽管多数病例在早期即被诊断，但仍存在一部分患者出现复发和转移，现有治疗方案对其效果有限。癌症干细胞在肿瘤发生、疾病进展、复发及转移过程中起关键作用，其高醛脱氢酶活性与侵袭性和化疗耐药性密切相关。因此，本研究旨在评估抑制ALDH对子宫内膜癌干细胞的影响。通过球体形成实验从ECC-1和RL95-2细胞系中分离获得子宫内膜癌干细胞，并从ALDH活性与表达、球体形成能力、自我更新能力、投影面积以及CD133、CD44、CD24和P53表达水平等方面评估ALDH抑制效果。采用基于质谱的蛋白质组学技术分析N,N-二乙氨基苯甲醛处理后的子宫内膜癌细胞蛋白质组特征。结果显示，DEAB能降低ALDH活性与表达，显著抑制球体形成能力并减小投影面积，同时上调CD133表达。此外，DEAB还能调控P53表达。蛋白质组学分析表明，经DEAB处理的子宫内膜癌细胞呈现独特的蛋白质组特征，共有75个上调蛋白和30个下调蛋白。综上所述，DEAB通过抑制ALDH活性与表达影响子宫内膜癌干细胞表型。ALDH18A1、SdhA和UBAP2L可作为子宫内膜癌潜在的新型分子靶点进行深入研究。
Influence of Aldehyde Dehydrogenase Inhibition on Stemness of Endometrial Cancer Stem Cells
肿瘤(癌症)患者之家