Department of Neurosurgery, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China.
ENT institute and Department of Otorhinolaryngology, Eye & ENT Hospital, Fudan University, Shanghai, 200031, China.
Mol Cell Endocrinol. 2021 Sep 15;535:111396. doi: 10.1016/j.mce.2021.111396. Epub 2021 Jul 13.
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.
尽管肿瘤干细胞样细胞 (TSLCs) 已在多种恶性肿瘤中进行了研究,但在垂体腺瘤中存在这些细胞的证据仍需要进一步探索。在这里,我们在大鼠泌乳素瘤 MMQ 细胞中鉴定出一小部分具有球体形成细胞特性的细胞,这些细胞对多巴胺激动剂治疗具有抵抗性。与 MMQ 细胞相比,球体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泌乳素 (PRL) 和多巴胺 2 受体 (D2R) 表达。相反,从这些细胞中分化出来的子肿瘤细胞恢复了对 DA 的敏感性,并表现出高表达的 PRL 和 D2R。较低的 D2R 表达和 DA 耐药性可能是由于 D2R 启动子的 DNA 高甲基化。我们的研究表明,从 MMQ 细胞中分离出的球体形成细胞具有 TSLCs 的特征,并对 DA 治疗具有抵抗性,这为进一步研究基于 TSLCs 的肿瘤复发机制提供了机会。