Role of Macrophage Migration Inhibitory Factor (MIF) in Melanoma

Abstract

Macrophage migration inhibitory factor (MIF) is an inflammatory cytokine involved in the carcinogenesis of many cancer types. Here, we review the published experimental and clinical data for MIF and its involvement in melanoma. All reported data show that MIF is overexpressed in melanoma cells, especially in case of metastatic disease. Clinical studies also indicate that high MIF expression is positively associated with aggressiveness of the disease. Some data also highlight the implication of MIF in angiogenesis, immunity and metastasis in melanoma cell lines, as well as the availability of different therapeutic options targeting MIF for the treatment of metastatic melanoma. Indeed, the main problem in metastatic melanoma is the lack of long-term effective treatment. This is linked to the capacity of melanoma cells to mutate very quickly and/or activate alternative signaling pathways. Thus, MIF targeting therapies could provide a new effective way of treating melanoma. Moreover, cell sensitivity to MIF depletion does not correlate with the BRAF mutational status. Regarding the fact that many melanoma patients carry a BRAF mutation, and that they develop resistance to BRAF inhibitors, this observation is very interesting as MIF inhibitors could be used to treat many patients in relapse after treatment with an inhibitor of the mutant BRAF protein.

The Role of Macrophage Migration Inhibitory Factor in Alzheimer′s Disease: Conventionally Pathogenetic or Unconventionally Protective?

“…MIF may also contribute to immunoinflammatory events during development of Duchenne s syndrome [37] and seems to play a pathogenetic role in major depressive disorders [38]. More recent studies also indicate that MIF is implicated in certain forms of cancer phenotypes such as melanoma, glioblastoma, prostate cancers, and neuroblastoma [39][40][41][42][43][44][45].…”

Emerging Role of the Macrophage Migration Inhibitory Factor Family of Cytokines in Neuroblastoma. Pathogenic Effectors and Novel Therapeutic Targets?

“…We and others have shown that MIF and DDT are involved in several diseases of different origins such as immunoinflammatory and autoimmune diseases, neurodegenerative and neuropsychiatric diseases, and cancer [24][25][26][27][28][29][30][31].…”

“…In addition, evidence generated during the last 15 years has also supported a pro-oncogenic role of MIF in certain types of cancers [29][30][31]. MIF may upregulate several tumorigenic processes, including tumor growth, invasiveness, and angiogenesis [32] primarily, but not exclusively, through its angiogenetic action, its AKT mediated antiapoptotic effects, and the inhibition of p53 function.…”

“…Numerous preclinical and clinical studies have demonstrated that MIF is overexpressed and may correlate with tumor aggressiveness in many different types of human cancers such as prostate , bladder, and kidney cancer [30], cervical cancer [20], ovarian cancer [44,45], breast cancer [29], gastric cancer [29], hepatocellular carcinoma [46], colon cancer [47,48], pancreatic cancer [49,50], gallbladder cancer [51], lung cancer [29,52], melanoma [31], head and neck cancer [29], acute myeloid leukemia [53,54], glioblastoma [15,55,56], and NB [57][58][59][60]. Moreover, elevated MIF expression is correlated with a worse patient overall survival in a large variety of cancers such as breast cancer [29], gastric cancer [29], hepatocellular carcinoma [61], pancreatic cancer [49,50], metastatic melanoma [31], head and neck cancer [29], esophageal squamous cell carcinoma [62], acute myeloid leukemia [53], glioblastoma [29,56], and NB [57].…”

Immunomodulatory Protective Effects of Rb9 Cyclic-Peptide in a Metastatic Melanoma Setting and the Involvement of Dendritic Cells

“…The macrophage migration inhibitory factor (MIF) is synthesized by epithelial and endothelial cells, T lymphocytes, macrophages, and by several tumors, particularly melanoma (35,36). MIF exerts its oncogenic effects through binding to CD74 receptor, CXCR4 chemokine receptor, and CD44, involved in MIF cellsignaling (37).…”