[Anoikis--a specific form of programmed cell death]

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.