25 Years On: A Retrospective on Migration Inhibitory Factor in Tumor Angiogenesis

Twenty-five years ago marked the publication of the first report describing a functional contribution by the cytokine, macrophage migration inhibitory factor (MIF), to tumor-associated angiogenesis and growth. Since first appearing, this report has been cited 304 times (as of this writing), underscoring not only the importance of this landmark study but also the importance of MIF in tumor neovascularization. Perhaps more importantly, this first link between MIF and stromal cell-dependent tumor angiogenesis presaged the subsequent identification of MIF in mediating protumorigenic contributions to several solid tumor stromal cell types, including monocytes, macrophages, T lymphocytes, NK cells, fibroblasts, endothelial progenitors and mesenchymal stem cells. This retrospective review will broadly evaluate both past and present literature stemming from this initial publication, with an emphasis on cellular sources, cellular effectors, signal transduction mechanisms and the clinical importance of MIF-dependent tumor vascularization.