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- W1981569661 abstract "Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, ILThe Macrophage Migration Inhibitory Factor (MIF) is overexpressed in many cancers and the degree of expression correlates with tumor aggressiveness. MIF contains a conserved tautomerase activity for which a physiological substrate or function has yet to be identified. We determined that sulforaphane (SFN), a chemopreventive agent prevalent in broccoli, covalently modifies MIF and inhibits its enzymatic tautomerase activity with an IC50 within the concentration range observed in the plasma of human subjects following a broccoli sprout meal. We are examining the role of MIF in tumor growth and metastasis in the 4T1 model of breast carcinoma. This model recapitulates many aspects of human breast tumor progression, including spontaneous metastasis from the mammary fat pad to similar target organs in similar proportions. We found that a 4T1 tumor cell line depleted of MIF forms smaller tumors than the 4T1 cells that express, and is reduced in its ability to metastasize to the lung. Reconstitution of the MIF deficient 4T1 cells with wild-type MIF rescues the defect in tumor growth and metastasis, while a tautomerase-deficient MIF does not. This suggests a function for the tautomerase activity in tumor progression and metastasis. Importantly, the MIF dependent growth differences are only manifested in vivo, as the MIF KD cell line is not compromised in growth or colony formation in vitro, suggesting that MIF may be contributing to the interaction between the tumor and the host immune response. This was confirmed by our demonstration that MIF deficient and MIF containing tumors exhibited similar growth properties in immunodeficient animals. This may represent an alternative mechanism for chemoprevention in which SFN can target the tumor microenvironment rather than the tumor cells. We are currently working to characterize a leukocyte population whose recruitment is altered in MIF depleted tumors.Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4369. doi:1538-7445.AM2012-4369" @default.
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- W1981569661 date "2012-04-15" @default.
- W1981569661 modified "2023-09-26" @default.
- W1981569661 title "Abstract 4369: The macrophage migration inhibitory factor (MIF) contributes to tumor growth and metastasis though interaction with the host immune response" @default.
- W1981569661 doi "https://doi.org/10.1158/1538-7445.am2012-4369" @default.
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