Department of Pathology and Laboratory Medicine, College of Medicine and University Hospitals, King Saud University, Riyadh 11461, Kingdom of Saudi Arabia.
Department of Basic Science, Biology Unit, Deanship of Preparatory Year and Supporting Studies, Imam Abdulrahman Bin Faisal University, Dammam 34212, Kingdom of Saudi Arabia.
Oncol Rep. 2018 Jun;39(6):2881-2891. doi: 10.3892/or.2018.6392. Epub 2018 Apr 23.
To date two questions that remain unanswered regarding cancer are the following: i) how is it initiated, and ii) what is the role that cancer stem cells (CSCs) play in the disease process? Understanding the biology of CSCs and how they are generated is pivotal for the development of successful treatment regimens. To date, the lack of a representative cell model has prevented the successful identification and eradication of CSCs in vivo. The current methods of CSC identification are dependent on the protocol used to generate these cells, which has introduced variation and made the identification process more complicated. Furthermore, the list of possible markers is increasing in complexity. This is further confounded by the fact that there is insufficient information to determine whether the cells these markers detect are truly self‑renewing stem cells or, instead, progenitor cells. In the present study, we investigated a novel cell line model, CSC480, which can be employed to assess CSC markers and for testing novel therapeutic regimens. CSC480 cells have been revealed to express markers of CSCs such as CD44, ALDH1 and Sox2, that have lower expression in the SW480 cell line. CSC480 cells also expressed higher levels of the cancer resistance marker, ABCG2 and had higher proliferative and growth capacity than SW480 cells. In the present study, we also evaluated a novel approach to identify different cell types present in heterogeneous cancer cell populations according to their proliferative ability using the proliferation marker 5‑ethynyl‑2'‑deoxyuridine (EdU). Furthermore, using EdU, we identified dormant cells with a modified label‑retaining cell (LRC) protocol. Through this novel LRC method, we assessed newly discovered markers of stemness to ascertain their capability to identify quiescent from dividing CSCs. In conclusion, the CSC480 cell line was an important model to be used in unravelling the underlying mechanisms that control fast‑dividing and partially self‑renewing stem cells (SCs) that may give rise to cancer.
迄今为止,癌症仍有两个未解之谜:i)癌症是如何发生的,ii)癌症干细胞(CSC)在疾病过程中扮演什么角色?了解 CSC 的生物学特性及其产生方式对于制定成功的治疗方案至关重要。迄今为止,由于缺乏代表性的细胞模型,CSC 在体内的成功鉴定和根除一直未能实现。目前的 CSC 鉴定方法依赖于生成这些细胞的方案,这引入了变化,使鉴定过程更加复杂。此外,可能的标记物清单变得越来越复杂。更复杂的是,事实是没有足够的信息来确定这些标记物检测到的细胞是否真的是自我更新的干细胞,还是祖细胞。在本研究中,我们研究了一种新型的细胞系模型 CSC480,该模型可用于评估 CSC 标记物和测试新的治疗方案。研究表明,CSC480 细胞表达 CSC 标志物,如 CD44、ALDH1 和 Sox2,其在 SW480 细胞系中的表达水平较低。CSC480 细胞还表达更高水平的癌症耐药标志物 ABCG2,并且比 SW480 细胞具有更高的增殖和生长能力。在本研究中,我们还评估了一种新方法,根据其增殖能力使用增殖标记物 5-乙炔基-2'-脱氧尿苷(EdU)来鉴定异质癌细胞群体中不同的细胞类型。此外,使用 EdU,我们使用改良的标记保留细胞(LRC)方案鉴定了休眠细胞。通过这种新的 LRC 方法,我们评估了新发现的干性标志物,以确定它们识别静止和分裂 CSC 的能力。总之,CSC480 细胞系是一个重要的模型,可用于揭示控制快速分裂和部分自我更新的干细胞(SCs)的潜在机制,这些干细胞可能引发癌症。