Engel Rebekah M, Chan Wing Hei, Nickless David, Hlavca Sara, Richards Elizabeth, Kerr Genevieve, Oliva Karen, McMurrick Paul J, Jardé Thierry, Abud Helen E
Department of Anatomy and Developmental Biology, Monash University, Clayton Victoria 3800, Australia.
Stem Cells and Development Program, Monash Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3800, Australia.
J Clin Med. 2020 Jan 2;9(1):128. doi: 10.3390/jcm9010128.
Colorectal cancer stem cells have been proposed to drive disease progression, tumour recurrence and chemoresistance. However, studies ablating leucine rich repeat containing G protein-coupled receptor 5 (LGR5)-positive stem cells have shown that they are rapidly replenished in primary tumours. Following injury in normal tissue, LGR5+ stem cells are replaced by a newly defined, transient population of revival stem cells. We investigated whether markers of the revival stem cell population are present in colorectal tumours and how this signature relates to chemoresistance. We examined the expression of different stem cell markers in a cohort of patient-derived colorectal cancer organoids and correlated expression with sensitivity to 5-fluorouracil (5-FU) treatment. Our findings revealed that there was inter-tumour variability in the expression of stem cell markers. Clusterin (, a marker of the revival stem cell population, was significantly enriched following 5-FU treatment and expression correlated with the level of drug resistance. Patient outcome data revealed that expression is associated with both lower patient survival and an increase in disease recurrence. This suggests that is a marker of drug resistance and may identify cells that drive colorectal cancer progression.
有人提出，结直肠癌干细胞会推动疾病进展、肿瘤复发和化疗耐药。然而，对富含亮氨酸重复序列的G蛋白偶联受体5（LGR5）阳性干细胞进行消融的研究表明，它们在原发性肿瘤中会迅速得到补充。在正常组织受到损伤后，LGR5+干细胞会被新定义的、短暂的复苏干细胞群体所取代。我们研究了复苏干细胞群体的标志物是否存在于结直肠癌肿瘤中，以及这种特征与化疗耐药性之间的关系。我们检测了一组患者来源的结直肠癌类器官中不同干细胞标志物的表达，并将表达情况与对5-氟尿嘧啶（5-FU）治疗的敏感性进行关联。我们的研究结果显示，干细胞标志物的表达在肿瘤之间存在差异。Clusterin（复苏干细胞群体的一种标志物）在5-FU治疗后显著富集，其表达与耐药水平相关。患者预后数据显示，其表达与患者较低的生存率以及疾病复发增加均相关。这表明Clusterin是耐药的一个标志物，可能识别出驱动结直肠癌进展的细胞。
