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Updated: Jul 19, 2026
Conditional Knockdown of Gene Expression in Cancer Cell Lines to Study the Recruitment of Monocytes/Macrophages to the Tumor Microenvironment
Published on: November 23, 2017
The p53-dependent effects of macrophage migration inhibitory factor revealed by gene targeting
G Fingerle-Rowson1, O Petrenko, C N Metz
1The Picower Institute for Medical Research, Manhasset, NY 11030, USA. g.fingerle-rowson@gmx.de
Abstract:
Macrophage migration inhibitory factor (MIF) is a mediator of host immunity and functions as a high, upstream activator of cells within the innate and the adaptive immunological systems. Recent studies have suggested a potentially broader role for MIF in growth regulation because of its ability to antagonize p53-mediated gene activation and apoptosis. To better understand MIF's activity in growth control, we generated and characterized a strain of MIF-knockout (MIF-KO) mice in the inbred, C57BL/6 background. Embryonic fibroblasts from MIF-KO mice exhibit p53-dependent growth alterations, increased p53 transcriptional activity, and resistance to ras-mediated transformation. Concurrent deletion of the p53 gene in vivo reversed the observed phenotype of cells deficient in MIF. In vivo studies showed that fibrosarcomas induced by the carcinogen benzo[alpha]pyrene are smaller in size and have a lower mitotic index in MIF-KO mice relative to their WT counterparts. The data provide direct genetic evidence for a functional link between MIF and the p53 tumor suppressor and indicate an important and previously unappreciated role for MIF in carcinogenesis.
Insights
Macrophage migration inhibitory factor (MIF) plays a role in tumor suppression. MIF knockout mice show reduced tumor growth, demonstrating MIF
Area of Science:
- Immunology
- Molecular Biology
- Oncology
Background:
- Macrophage migration inhibitory factor (MIF) is a key immune mediator.
- Emerging evidence suggests MIF's involvement in growth regulation, potentially by antagonizing p53.
- Understanding MIF's role in cell growth and cancer is crucial.
Purpose of the Study:
- To investigate the role of MIF in growth control and carcinogenesis.
- To elucidate the functional relationship between MIF and the p53 tumor suppressor pathway.
Main Methods:
- Generation and characterization of Macrophage migration inhibitory factor-knockout (MIF-KO) mice.
- Analysis of embryonic fibroblasts for growth alterations and p53 activity.
- In vivo studies using carcinogen-induced fibrosarcomas in MIF-KO and wild-type (WT) mice.
Main Results:
- MIF-KO fibroblasts display p53-dependent growth alterations and resistance to transformation.
- Deletion of p53 reversed the phenotype in MIF-deficient cells.
- MIF-KO mice exhibited smaller induced fibrosarcomas with a lower mitotic index compared to WT mice.
Conclusions:
- Direct genetic evidence confirms a functional link between MIF and the p53 tumor suppressor.
- MIF plays a significant, previously unrecognized role in carcinogenesis.
- Targeting MIF may offer novel therapeutic strategies for cancer.
