The Role of Leukemia Inhibitory Factor in Cancer and Cancer Metastasis

Abstract

Leukemia inhibitory factor (LIF) is a cytokine that exerts pleiotropic activities. LIF is a member of the interleukin-6 family of cytokines which share a similar receptor complex and signal through the gp 130 receptor subunit. Several neoplastic cells originating from various tissues express either LIF, its receptor, or both and respond to this cytokine. Data accumulated thus far provide a complex picture of LIF activities with LIF being stimulatory, inhibitory or having no effect, depending on the system in which it is studied. LIF appears to play an important role in stimulating the growth of certain tumours, and in affecting the surrounding tissue and the target organ of tumour metastases, particularly bone and skeletal tissue. Overproduction of LIF is likely to have significant constitutional effects. Studies using animal models have shown that LIF induces cachexia, metastatic-type bone calcifications, thrombocytosis, and an abnormal immune response. It is therefore possible that suppression of LIF activity might have a beneficial effect in some cancer patients.