Macrophage migration inhibitory factor is differentially expressed in normal and choriocarcinoma trophoblast cells

Abstract

Trophoblast cells are specific for placenta, the organ necessary for development of the fetus. Trophoblast derived choriocarcinoma is a rare cancer, with high metastatic potential, invading surrounding tissues and distant organs. Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine involved in a wide range of biological processes, which is increased in almost all human cancers. Expression of MIF in normal and choriocarcinoma trophoblast cells is investigated here, using normal extravillous trophoblast derived cell line HTR-8/SVneo, and choriocarcinoma cell lines JAR and JEG3. Expression of MIF and its receptors CD74 and CXCR2 was investigated at mRNA level using qPCR. Expression of MIF protein was studied using immunofluorescence and western blot, under reducing and native conditions, in whole cell lysates, subcellular fractions and conditioned media. The expression of MIF mRNA was similar in all three cell lines, while CD74 mRNA was more expressed in choriocarcinoma cells (14-fold for JAR, 12-fold for JEG3, p<0.01). CXCR2 mRNA was higher in JEG3 cell line compared to HTR-8/SVneo cells (6-fold, p<0.01). While the cellular level of MIF was similar, the level of secreted MIF was lower in JAR cell conditioned media compared to media of both HTR-8/SVneo (2.8-fold, p<0.01) and JEG3 cells (4.1-fold, p<0.001). Cellular distribution of MIF was similar between the studied cell types. MIF was predominantly cytoplasmic, but also detected in membrane, nuclear soluble and nuclear chromatin fraction. MIF appeared in high molecular weight complexes of >150 kDa under native conditions. A band of 140-145 kDa was consistently present in JEG3 cell lysates, while it was absent or very weak in other cell types. These results show that MIF/CD74 axis is shifted in choriocarcinoma, as previously shown for other cancers, and further justifies research towards the most effective MIF targeting therapeutics.

Role of the Macrophage Migration Inhibitory Factor in the Pathophysiology of Pre-Eclampsia

“…The same research group also studied the potential contribution of trophoblast MIF on the spiral artery remodeling process. They demonstrated that attenuation of endogenous MIF by specific siRNA had a negative effect on the ability of HTR-8/SVneo to differentiate into endothelial-like phenotype [ 111 ]. HTR-8/SVneo cells also produce MIF in response to LPS, a cell wall constituent of most Gram-negative bacteria recognized by TLR4 [ 121 ].…”

Macrophage migration inhibitory factor (MIF) predicts survival in patients with clear cell renal cell carcinoma

“…The overexpression of MIF present in tumors not only confers an advantage in tumor growth but also confers a particular aggressiveness to tumor cells, allowing them to migrate and metastasize. The relationship between the MIF factor and tumorigenesis has been confirmed in various malignancies [ 6 , 8 ]. The level of MIF expression in most cancers correlates with tumor progression and the ability of cancer cells to spread [ 9 ].…”

α-Solanine Inhibits Proliferation, Invasion, and Migration, and Induces Apoptosis in Human Choriocarcinoma JEG-3 Cells In Vitro and In Vivo

“…Human placenta choriocarcinoma is a highly malignant trophoblastic tumor characterized by abnormal trophoblastic hyperplasia, the absence of chorionic villi, hemorrhage, necrosis, and high metastatic potential [1,2]. Choriocarcinoma is a very rare neoplasm.…”