Mechanisms and effectors of MIF-dependent promotion of tumourigenesis

The importance of secreted cytokines and growth factors in the development and promotion of malignancies is often underestimated. Many different soluble, extracellular gene products participate in processes that collectively contribute to the growth and survival of a developing neoplasm. These secreted molecules can, directly or indirectly, play a central role in uncontrolled tumour cell division, angiogenic stimulation or suppression of tumour cell immune surveillance. One of the first cytokine activities ever described, macrophage migration inhibitory factor (MIF), is unique to these soluble mediators in that it participates in all of these pro-tumourigenic processes. Overexpressed in most tumour types examined, MIF has been shown to promote malignant cell transformation, inhibit tumour cell-specific immune cytolytic responses and strongly enhance neovascularization. Despite this broad array of activities, the elucidation of molecular and cellular mechanisms involved in MIF-dependent bioactions has remained elusive. This review will focus on recently characterized phenotypes and mechanistic effectors thought to be associated with MIF-dependent promotion of neoplastic processes and discuss their relative importance in carcinogenesis.