Leukemia inhibitory factor (LIF): A growth factor with pleiotropic effects on bone biology

Historically, growth factors are denominated based on a specific biological activity. In many cases, these factors display a much broader spectrum of activities, especially when their effect is tested on various cell or tissue types. Consequently, names of certain factors are quite deceptive. A textbook example is leukemia inhibitory factor (LIF). LIF was initially described based on its ability to induce differentiation in the murine myeloid leukemia cell line M1. Later, LIF turned out to be a synonym for at least nine different factors defined on the basis of their effects on a variety of cell types including lymphomas, liver cells, embryonic stem cells and carcinoma cells, neurons, melanomas and osteoclasts. Apart from its differential effect on unrelated cell types and tissues, LIF induces biphasic effects on cells of the same “lineage” as well. Needless to say, LIF activity in these circumstances largely depends on the developmental stage of the target cells. An example is LIF activity on bone cells. Osteoclast as well as osteoblast activity is stimulated or suppressed by LIF depending on the developmental stage of the respective cells. This concept is of utmost importance in the evaluation of the seemingly opposing or contradictory effects of LIF in vitro as well as in vivo.