Alanko T, Tienari J, Lehtonen E, Saksela O
Department of Virology, Haartman Institute, University of Helsinki, Finland.
Exp Cell Res. 1996 Nov 1;228(2):306-12. doi: 10.1006/excr.1996.0330.
Tera-2 is a human teratocarcinoma cell line, which is induced to differentiate into neuronal direction by retinoic acid. Once differentiated, the cells form an almost nondividing population that can be maintained for weeks under conventional culture conditions. If differentiation by retinoic acid is induced while the cells are growing on type I collagen or if the already-differentiated cells are transferred onto collagen, they survive only a few days unless the cultures are repeatedly supplied with FGF-2. Lack of this growth factor induces programmed cell death (apoptosis) detectable after 24-48 h, as marked by DNA cleavage and nuclear fragmentation. The undifferentiated stem cells survive and proliferate readily on collagen without addition of FGF-2. Tera-2 cells express two members of the FGF family, FGF-2 and FGF-4. The expression of both FGFs is turned off during differentiation on collagen substratum, whereas when cultivated on plain tissue culture dish, the expression of only FGF-4 becomes undetectable. The results indicate that signaling through cell surface FGF receptors is vital for the cells, and differentiation on collagen substratum results in complete extinction of the autocrine stimulatory loop. In vivo, such induction of growth factor dependency upon differentiation would result in apoptotic death of those cells which fail to find adequate conditions for continuing FGF stimulation.
Tera-2是一种人畸胎瘤细胞系，可被视黄酸诱导向神经元方向分化。一旦分化，这些细胞就会形成一个几乎不分裂的群体，在常规培养条件下可以维持数周。如果在细胞在I型胶原上生长时用视黄酸诱导分化，或者如果将已经分化的细胞转移到胶原上，除非培养基反复添加FGF-2，否则它们只能存活几天。缺乏这种生长因子会诱导程序性细胞死亡（凋亡），在24-48小时后可检测到，表现为DNA裂解和核碎片化。未分化的干细胞在不添加FGF-2的情况下能在胶原上轻松存活和增殖。Tera-2细胞表达FGF家族的两个成员，FGF-2和FGF-4。在胶原基质上分化过程中，两种FGF的表达都关闭，而当在普通组织培养皿上培养时，只有FGF-4的表达变得不可检测。结果表明，通过细胞表面FGF受体的信号传导对细胞至关重要，并且在胶原基质上的分化导致自分泌刺激环完全消失。在体内，这种对分化的生长因子依赖性诱导将导致那些未能找到持续FGF刺激的适当条件的细胞发生凋亡死亡。
