induce proliferation, inhibit proliferation or cause apoptosis, depending on the system in which this cytokine is studied. Several studies have shown that LIF's divergent physiological effects have been adopted by a variety of neoplastic cells and that LIF takes part in the pathophysiology of cancer. In many neoplasms LIF, produced by either normal tissue or tumour cells, provides the cancerous process with growth and survival advantage.
LIF was initially characterized by its ability to induce differentiation of the
W.G. Jiang et al. (eds.), Growth Factors and their Receptors in Cancer Metastasis, 1-25. © 2001 Kluwer Academic Publishers. Printed in the Netherlands.
murine myeloid leukemia cell line M1 (10-15) and was cloned from a murine T-cell library (12,16). Independently, a human molecule in the supernatant of T-cell clones was identified and termed human interleukin for DA cells (HILDA) (17-20). Once cloned, this molecule was found to be homologous to its murine counterpart (21-23). Subsequently, additional characteristics of LIF were described, and it was given several other names, including differentiation factor (D-factor) (24-25), differentiation-inducing factor (DIF) (26), differentiation inhibitory activity (DIA) (27), differentiation-retarding factor (DRF) (27,28), hepatocyte-stimulating factor III (HSF III) (29), melanoma-derived lipoprotein lipase inhibitor I (MLPLI) (34), cholinergic neural differentiation factor (31), and osteoclast-activating factor (OAF) (26,32) (Table 1). However, because LIF exerts a broad spectrum of activities and despite its diverse and sometimes opposing effects on different leukemia cell lines (21,26,27,29,32,3335), LIF has become the official name of this cytokine (1).
The effects of LIF on various tissues provide several clues to its possible role in cancer. For example, LIF stimulates embryonic stem cell proliferation (36-40). It affects blastocyst implantation (36-41) and influences the development of peripheral nerves from their precursors in the embryonic neural crest (32,42), which implies that LIF can stimulate immature cells and probably tumour cells with immature cell characteristics. In addition, LIF was shown to induce a catabolic state and cachexia in nude mice and in primates (43-45). It stimulated the release of acute-phase proteins from hepatocytes, (45-47) and affected bone metabolism by inducing both osteoblastic and osteoclastic activities (48-52). These effects are characteristic clinical features of patients with neoplastic diseases likely to be induced by various cytokines including LIF.
In this chapter we describe the physiological characteristics and the pathophysiological role of LIF in cancer and cancer metastasis.
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