Faculty of Dentistry, National University of Singapore, Singapore.
J Oral Pathol Med. 2013 Oct;42(9):682-90. doi: 10.1111/jop.12076. Epub 2013 Apr 30.
There is now substantial evidence that only a subpopulation of cells in solid cancers is able to sustain tumour growth and to re-initiate new tumours. Various cancers and cancer-derived cell lines, including head and neck squamous cell carcinomas (HNSCC), have a subpopulation of cancer stem cells (CSCs), marked by high levels of expression of the CD44 adhesion molecule. However, it has been unclear whether, in addition to acting as a marker, CD44 has functions that directly influence stem cell properties. The aim of this study was to investigate the role of CD44 in the maintenance of the CSC population in HNSCC cell lines.
CD44 was down-regulated either by treating cultures with 1 mM sodium butyrate or by the more specific method of knockdown with siRNAs directed against CD44. Changes in CD44 expression levels were assessed at the mRNA and protein levels, and the effects of CD44 down-regulation on cell proliferation and on the fate of the CSC subpopulations were assessed.
Reduced CD44 expression resulted in a decreased rate of population expansion, both initially and on repassage, and there was an alteration in colony morphologies indicative of stem cell loss. Down-regulation of CD44 also led to reduced expression of Oct4A, an alternative marker of CSCs.
The results suggest that CD44 has a functional role in maintaining stem cell properties in HNSCC cell lines and provides support for the concept that therapies targeting CD44, or its related signalling pathways, may allow development of more efficient treatment strategies.
现在有大量证据表明，只有实体瘤中的一小部分细胞能够维持肿瘤生长并重新引发新的肿瘤。各种癌症和癌细胞系，包括头颈部鳞状细胞癌（HNSCC），都有一小部分癌症干细胞（CSC），其特征是高水平表达 CD44 粘附分子。然而，尚不清楚 CD44 是否除了作为标志物之外，还具有直接影响干细胞特性的功能。本研究旨在研究 CD44 在维持 HNSCC 细胞系中的 CSC 群体中的作用。
通过用 1mM 丁酸钠处理培养物或用针对 CD44 的 siRNA 进行更特异性的敲低来下调 CD44。在 mRNA 和蛋白质水平上评估 CD44 表达水平的变化，并评估 CD44 下调对细胞增殖和 CSC 亚群命运的影响。
降低 CD44 表达导致群体扩张速度降低，无论是最初还是再传代时，并且集落形态发生变化，表明干细胞丢失。CD44 的下调也导致 CSC 的替代标志物 Oct4A 的表达降低。
结果表明 CD44 在维持 HNSCC 细胞系中的干细胞特性方面具有功能作用，并为靶向 CD44 或其相关信号通路的治疗方法可能允许开发更有效的治疗策略的概念提供支持。
