2024 World Conference on Lung Cancer (WCLC) - ePosters-EP.02D.01 Macrophage Migration Inhibitory Factor Promotes Invasion and Epithelial to Mesenchymal Transition in Lung Adenocarcinoma

EP.02D.01 Macrophage Migration Inhibitory Factor Promotes Invasion and Epithelial to Mesenchymal Transition in Lung Adenocarcinoma

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This study investigates the role of Macrophage Migration Inhibitory Factor (MIF) in lung adenocarcinoma, focusing on its influence within the tumor microenvironment (TME) and its impact on cancer progression and treatment resistance. Previous research identified MIF as a gene linked to recurrence-free survival, suggesting its potential importance in tumor biology.<br /><br />The researchers found that MIF is overexpressed in lung adenocarcinoma and plays a crucial role in promoting invasion and epithelial-to-mesenchymal transition (EMT), processes that facilitate cancer metastasis. MIF enhances these processes through the c-JUN/SLUG/N-cadherin pathway, which increases the expression of matrix metalloproteinases MMP-2 and MMP-9, enzymes involved in tissue remodeling and tumor invasion.<br /><br />The study also highlights MIF's role in conferring resistance to cisplatin, a common chemotherapy drug. Using the MIF inhibitor Ibudilast, researchers were able to downregulate MIF expression, leading to a decrease in phosphorylated ERK—a protein involved in cell signaling associated with cancer cell proliferation.<br /><br />Experiments with lung adenocarcinoma cell lines A549 and H1975 demonstrated endogenous upregulation of MIF, which could be effectively downregulated using lentiviral transfection techniques. The use of Ibudilast not only reduced cellular proliferation, invasion, migration, and colony formation but also increased the cells' sensitivity to cisplatin, suggesting potential therapeutic benefits.<br /><br />Overall, this research suggests that targeting MIF could be a viable strategy to inhibit tumor progression and enhance the effectiveness of existing chemotherapy treatments in lung adenocarcinoma. This study was partly supported by the NIH and the Stephen J. Solarz Memorial Fund, with acknowledgments that findings and opinions do not necessarily represent official U.S. government policies.

Asset Subtitle

Shamus Carr

Meta Tag

Speaker Shamus Carr

Topic Tumor Biology – Preclinical Biology

Keywords

Macrophage Migration Inhibitory Factor

lung adenocarcinoma

tumor microenvironment

cancer progression

treatment resistance

epithelial-to-mesenchymal transition

c-JUN/SLUG/N-cadherin pathway

cisplatin resistance

Ibudilast

therapeutic strategy