Department of Experimental Medicine & Biotechnology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India.
Pathol Oncol Res. 2020 Jan;26(1):371-378. doi: 10.1007/s12253-018-0503-8. Epub 2018 Oct 25.
In view of popularity of cancer stem cell (CSC) model all events in evolution of cancer are being explained in that context. Breast cancer is first solid tumor in which CSCs were identified. We aimed to compare stemness profile of two major subtypes [Estrogen receptor positive (ER) and negative (ER)] breast cancer using different sets of markers. Expression of CD44/CD24, CK/Vimentin, E-Cadherin/Fibronectin and percentage of side population (SP) was studied in ER (T47D) and ER (MDA-MB-231) cell lines by flow cytometry. Breast CSCs (BCSCs) were sorted using CD44/CD24 expression and SP analysis and cultured. BCSCs were then compared with Non-CSCs (NCSCs) for response to drugs (Paclitaxel and Cisplatin), Ki67 and ER expression. Results showed higher expression of stemness markers (CD44/CD24, CK/Vimentin and E-Cadherin/Fibrinectin) in MDA-MB-231 cells. Percentage SP representing BCSCs was found to be significantly more in later (3.20 ± 0.002 cf. T47D 1.25% ± 0.0007). BCSCs were found to be more resistant to drugs as compared to NCSCs in both cell lines. ER expression was weak in BCSCs sorted from T47D as compared to NCSCs. Ki67 was expressed in both BCSCs and NCSCs. Differences in expression of stemness markers help to explain aggressive behavior, higher recurrence rate and metastatic potential of MDA-MB-231 cells. However, no correlation amongst different markers used suggests that they may be identifying varied populations of cells in tumor hierarchy. A weak ER expression in BCSCs may be strategy used by BCSCs to escape effect of hormone therapy in ER breast cancers.
鉴于癌症干细胞(CSC)模型的普及,所有癌症演化过程中的事件都在该框架下得到了解释。乳腺癌是第一个被鉴定出 CSCs 的实体肿瘤。我们旨在使用不同的标志物集来比较两种主要亚型(雌激素受体阳性(ER)和阴性(ER))乳腺癌的干性特征。通过流式细胞术研究 ER(T47D)和 ER(MDA-MB-231)细胞系中 CD44/CD24、CK/Vimentin、E-Cadherin/Fibronectin 的表达和侧群(SP)的百分比。使用 CD44/CD24 表达和 SP 分析对乳腺 CSCs(BCSCs)进行分选,并进行培养。然后将 BCSCs 与非 CSCs(NCSCs)进行比较,以评估对药物(紫杉醇和顺铂)、Ki67 和 ER 表达的反应。结果显示,MDA-MB-231 细胞中干性标志物(CD44/CD24、CK/Vimentin 和 E-Cadherin/Fibronectin)的表达更高。SP 代表的 BCSC 百分比在后一种细胞中明显更高(3.20±0.002,相比之下,T47D 为 1.25%±0.0007)。与 NCSCs 相比,两种细胞系中的 BCSCs 对药物的耐药性更高。与 NCSCs 相比,从 T47D 分选的 BCSCs 中 ER 表达较弱。Ki67 在 BCSCs 和 NCSCs 中均有表达。干性标志物表达的差异有助于解释 MDA-MB-231 细胞的侵袭性行为、更高的复发率和转移潜能。然而,不同标志物的表达差异表明,它们可能识别肿瘤层次结构中不同的细胞群体。BCSCs 中 ER 表达较弱可能是 BCSCs 逃避 ER 乳腺癌激素治疗作用的策略。