高度增殖性、癌症干细胞样和天然永生化三阴性乳腺癌细胞系 KAIMRC2 的分离和建立。
Isolation and Establishment of a Highly Proliferative, Cancer Stem Cell-Like, and Naturally Immortalized Triple-Negative Breast Cancer Cell Line, KAIMRC2.
机构信息
King Abdullah International Medical Research Center (KAIMRC), Medical Research Core Facility and Platforms (MRCFP), King Saud bin Abdulaziz University for Health Sciences (KSAU-HS), Ministry of National Guard Health Affairs (MNGHA), Riyadh 11481, Saudi Arabia.
Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.
出版信息
Cells. 2021 May 24;10(6):1303. doi: 10.3390/cells10061303.
In vitro studies of a disease are key to any in vivo investigation in understanding the disease and developing new therapy regimens. Immortalized cancer cell lines are the best and easiest model for studying cancer in vitro. Here, we report the establishment of a naturally immortalized highly tumorigenic and triple-negative breast cancer cell line, KAIMRC2. This cell line is derived from a Saudi Arabian female breast cancer patient with invasive ductal carcinoma. Immunocytochemistry showed a significant ratio of the KAIMRC2 cells' expressing key breast epithelial and cancer stem cells (CSCs) markers, including CD47, CD133, CD49f, CD44, and ALDH-1A1. Gene and protein expression analysis showed overexpression of ABC transporter and AKT-PI3Kinase as well as JAK/STAT signaling pathways. In contrast, the absence of the tumor suppressor genes p53 and p73 may explain their high proliferative index. The mice model also confirmed the tumorigenic potential of the KAIMRC2 cell line, and drug tolerance studies revealed few very potent candidates. Our results confirmed an aggressive phenotype with metastatic potential and cancer stem cell-like characteristics of the KAIMR2 cell line. Furthermore, we have also presented potent small molecule inhibitors, especially Ryuvidine, that can be further developed, alone or in synergy with other potent inhibitors, to target multiple cancer-related pathways.
体外研究是理解疾病和开发新治疗方案的任何体内研究的关键。永生化癌细胞系是体外研究癌症的最佳和最简单模型。在这里,我们报告了一种天然永生化的高致瘤性和三阴性乳腺癌细胞系 KAIMRC2 的建立。该细胞系源自一名沙特阿拉伯女性乳腺癌患者的浸润性导管癌。免疫细胞化学显示,KAIMRC2 细胞表达关键的乳腺上皮和癌症干细胞(CSCs)标志物的比例显著,包括 CD47、CD133、CD49f、CD44 和 ALDH-1A1。基因和蛋白表达分析显示 ABC 转运体和 AKT-PI3K 信号通路以及 JAK/STAT 信号通路的过度表达。相比之下,肿瘤抑制基因 p53 和 p73 的缺失可能解释了它们高增殖指数的原因。小鼠模型也证实了 KAIMRC2 细胞系的致瘤潜力,药物耐受研究揭示了少数非常有效的候选药物。我们的结果证实了 KAIMR2 细胞系具有侵袭性表型、转移潜力和癌症干细胞样特征。此外,我们还提出了一些有效的小分子抑制剂,特别是 Ryuvidine,这些抑制剂可以单独或与其他有效的抑制剂联合开发,以针对多种与癌症相关的途径。