Although tumor stem-like cells (TSLCs) have been studied in a range of malignant tumors, evidence for the presence of these cells in pituitary adenomas needs further exploration. Here, we identified a small subset of sphere-forming cells possess tumor stem-like cell properties in rat prolactinoma MMQ cells, which resist to dopamine agonist treatment. Comparing to MMQ cells, sphere-forming cells showed higher cell viability after dopamine agonist (DA) treatment. Furthermore, the cells showed lower expression of prolactin (PRL) and dopamine 2 receptor (D2R). On the contrary, the daughter tumor cells differentiated from these cells restored the sensitivity to DA and showed high expression of PRL and D2R. The lower D2R expression and DA resistance might be due to DNA hypermethylation of D2R promoter. Our study demonstrates that the sphere-forming cells isolated from MMQ cells possess the trait of TSLCs and resist to DA treatment, which offers the opportunity to further investigate the mechanisms underlying tumor recurrence based on TSLCs.

尽管已经在一系列恶性肿瘤中研究了肿瘤干细胞样细胞（TSLC），但垂体腺瘤中存在这些细胞的证据需要进一步探索。在这里，我们确定了一小部分球形成细胞在大鼠泌乳素瘤 MMQ 细胞中具有肿瘤干细胞样细胞特性，这些细胞对多巴胺激动剂治疗有抵抗力。与 MMQ 细胞相比，球形成细胞在多巴胺激动剂 (DA) 处理后表现出更高的细胞活力。此外，这些细胞表现出较低的催乳素 (PRL) 和多巴胺 2 受体 (D2R) 表达。相反，从这些细胞分化的子肿瘤细胞恢复了对DA的敏感性并显示出PRL和D2R的高表达。较低的 D2R 表达和 DA 抗性可能是由于 D2R 启动子的 DNA 高甲基化。