LIF derives its name from its ability to induce the terminal differentiation of myeloid leukemic cells, thus preventing their continued growth. Other properties attributed to the cytokine include: the growth promotion and cell differentiation of different types of target cells, influence on bonemetabolism, cachexia, neural development, embryogenesis and inflammation. p53 regulated LIF has been shown to facilitate implantation in the mouse model and possibly in humans. It has been suggested that recombinant human LIF might help to improve the implantation rate in women with unexplained infertility.
LIF is normally expressed in the trophectoderm of the developing embryo, with its receptor LIFR expressed throughout the inner cell mass. As embryonic stem cells are derived from the inner cell mass at the blastocyst stage, removing them from the inner cell mass also removes their source of LIF. Recombinant LIF has been produced in plants by InVitria.
Removal of LIF pushes stem cells toward differentiation, but they retain their proliferative potential or pluripotency. Therefore LIF is used in mouse embryonic stem cell culture. It is necessary to maintain the stem cells in an undifferentiated state, however genetic manipulation of embryonic stem cells allows for LIF independent growth, notably overexpression of the gene Nanog.
LIF is typically added to stem cell culture medium to reduce spontaneous differentiation.
Králícková M, Síma P, Rokyta Z (2005). "Role of the leukemia-inhibitory factor gene mutations in infertile women: the embryo-endometrial cytokine cross talk during implantation--a delicate homeostatic equilibrium". Folia Microbiol. (Praha)50 (3): 179–86. doi:10.1007/BF02931563. PMID16295654.
Stahl J, Gearing DP, Willson TA, et al. (1990). "Structural organization of the genes for murine and human leukemia inhibitory factor. Evolutionary conservation of coding and non-coding regions". J. Biol. Chem.265 (15): 8833–41. PMID1692837.
Lowe DG, Nunes W, Bombara M, et al. (1989). "Genomic cloning and heterologous expression of human differentiation-stimulating factor". DNA8 (5): 351–9. doi:10.1089/dna.1.1989.8.351. PMID2475312.
Sutherland GR, Baker E, Hyland VJ, et al. (1989). "The gene for human leukemia inhibitory factor (LIF) maps to 22q12". Leukemia3 (1): 9–13. PMID2491897.
Mori M, Yamaguchi K, Abe K (1989). "Purification of a lipoprotein lipase-inhibiting protein produced by a melanoma cell line associated with cancer cachexia". Biochem. Biophys. Res. Commun.160 (3): 1085–92. doi:10.1016/S0006-291X(89)80114-7. PMID2730639.
Williams RL, Hilton DJ, Pease S, et al. (1989). "Myeloid leukaemia inhibitory factor maintains the developmental potential of embryonic stem cells". Nature336 (6200): 684–7. doi:10.1038/336684a0. PMID3143916.
Moreau JF, Donaldson DD, Bennett F, et al. (1989). "Leukaemia inhibitory factor is identical to the myeloid growth factor human interleukin for DA cells". Nature336 (6200): 690–2. doi:10.1038/336690a0. PMID3143918.
Yamaguchi M, Miki N, Ono M, et al. (1995). "Inhibition of growth hormone-releasing factor production in mouse placenta by cytokines using gp130 as a signal transducer". Endocrinology136 (3): 1072–8. doi:10.1210/en.136.3.1072. PMID7867561.
Schmelzer CH, Harris RJ, Butler D, et al. (1993). "Glycosylation pattern and disulfide assignments of recombinant human differentiation-stimulating factor". Arch. Biochem. Biophys.302 (2): 484–9. doi:10.1006/abbi.1993.1243. PMID8489250.
Aikawa J, Ikeda-Naiki S, Ohgane J, et al. (1997). "Molecular cloning of rat leukemia inhibitory factor receptor alpha-chain gene and its expression during pregnancy". Biochim. Biophys. Acta1353 (3): 266–76. doi:10.1016/s0167-4781(97)00079-1. PMID9349722.
Tanaka M, Hara T, Copeland NG, et al. (1999). "Reconstitution of the functional mouse oncostatin M (OSM) receptor: molecular cloning of the mouse OSM receptor beta subunit". Blood93 (3): 804–15. PMID9920829.