Rosner Guy
Department of Internal Medicine H, Gastroenterology Department, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
Harefuah. 2003 Dec;142(12):857-61, 876.
Cell therapy, in particular liver cell transplantation, holds great therapeutic potential and is partially hindered by the high rate of apoptosis during cell isolation, cryopreservation and engraftment. Apoptosis triggered by cell detachment from the extracellular matrix, which occurs during hepatocyte isolation, is a phenomenon termed "anoikis". It's importance in the normal physiologic development of the human body, as well as in disease states, has been described. Cancer cells harbor anoikis resistance allowing spread to occur. Activation of the protein Fas associated death domain/MORT1 initiates the apoptosis cascade, with further downstream activation of caspase 8, Bid, cytochrome c and the executioner caspases. The anti-apoptotic protein family (bcl-2) and integrins, in particular beta 1 integrin, balance the pro apoptotic signals. The family of caspase enzymes, currently including 14 members, is subdivided by the prodomain length, specific substrate and phylogenetic analysis, and plays a crucial role in the apoptotic cascade. Therefore, understanding the molecular biology of apoptosis and specifically the "form" termed anoikis, has advanced clinical implications in cancer and cell therapy research.
细胞疗法,尤其是肝细胞移植,具有巨大的治疗潜力,但在细胞分离、冷冻保存和植入过程中,高凋亡率在一定程度上阻碍了其发展。在肝细胞分离过程中,细胞从细胞外基质脱离引发的凋亡,是一种被称为“失巢凋亡”的现象。它在人体正常生理发育以及疾病状态中的重要性已被描述。癌细胞具有失巢凋亡抗性,从而得以扩散。蛋白Fas相关死亡结构域/MORT1的激活启动凋亡级联反应,进一步下游激活半胱天冬酶8、Bid、细胞色素c和执行性半胱天冬酶。抗凋亡蛋白家族(bcl-2)和整合素,尤其是β1整合素,平衡促凋亡信号。目前包括14个成员的半胱天冬酶家族,根据前结构域长度、特定底物和系统发育分析进行细分,在凋亡级联反应中起关键作用。因此,了解凋亡的分子生物学,特别是“失巢凋亡”这种形式,在癌症和细胞疗法研究中具有重要的临床意义。