Yasumoto S, Kunimura C, Kikuchi K, Tahara H, Ohji H, Yamamoto H, Ide T, Utakoji T
Laboratory of Molecular Cell Biology, Kanagawa Cancer Center Research Institute, Yokohama, Japan.
Oncogene. 1996 Jul 18;13(2):433-9.
Telomerase activity is found in most cancer tissues and many immortalized cell lines as well as in germ line cells but it is generally undetected in normal human somatic tissues. There is weak telomerase activity in some cell types of hematopoietic lineage in which a stem cell-like subpopulation may exist. Likewise, physiologically regenerating somatic tissues and organs such as skin, small intestine, and most other epithelia of the human body are supposed to contain similar cell lineages to maintain their renewal throughout the life span of individuals. It is therefore of interest whether telomerase activity is present in physiologically regenerating epithelial cells. Telomerase activity was detected, though very weakly, in cultured normal epidermal keratinocytes and at higher levels in a subpopulation that adhere rapidly on collagen IV-coated culture dishes. No telomerase activity was detected in a subpopulation that was less adherent on the coated dishes. The rapidly adherent subpopulation of keratinocytes was enriched in small proliferating cells with macrocolony forming potential. It was also passaged through more generations in culture, and expressed integrin beta 1 at higher levels than the less adherent subpopulation. Telomerase activity was similarly found in ectocervical keratinocytes as well as in simple endocervical epithelial cells. These findings provide the evidence of a telomerase-positive population among physiologically regenerating normal human epithelial cells. The identity of the telomerase-positive cells remains to be defined.
端粒酶活性在大多数癌症组织、许多永生化细胞系以及生殖系细胞中均有发现,但在正常人体体细胞组织中通常检测不到。在造血谱系的某些细胞类型中存在微弱的端粒酶活性,其中可能存在类似干细胞的亚群。同样,生理上正在再生的体细胞组织和器官,如皮肤、小肠以及人体的大多数其他上皮组织,被认为含有类似的细胞谱系,以在个体的整个生命周期中维持其更新。因此,生理上正在再生的上皮细胞中是否存在端粒酶活性是一个值得关注的问题。在培养的正常表皮角质形成细胞中检测到了端粒酶活性,尽管非常微弱,而在胶原IV包被的培养皿上快速黏附的亚群中其活性水平更高。在包被培养皿上黏附性较差的亚群中未检测到端粒酶活性。角质形成细胞的快速黏附亚群富含具有大克隆形成潜力的小增殖细胞。它在培养中传代次数更多,并且比黏附性较差的亚群表达更高水平的整合素β1。在宫颈外角质形成细胞以及宫颈内简单上皮细胞中也同样发现了端粒酶活性。这些发现为生理上正在再生的正常人体上皮细胞中存在端粒酶阳性群体提供了证据。端粒酶阳性细胞的身份仍有待确定。