Macrophage Migration Inhibitory Factor Promotes Tumor Growth in the Context of Lung Injury and Repair

Division of Pulmonary and Critical Care Medicine, University of Michigan Medical Center, Ann Arbor, Michigan 48109-0642, USA.
American Journal of Respiratory and Critical Care Medicine (Impact Factor: 13). 10/2010; 182(8):1030-7. DOI: 10.1164/rccm.201001-0120OC
Source: PubMed


Tissue injury and repair involve highly conserved processes governed by mechanisms that can be co-opted in tumors. We hypothesized that soluble factors released during the repair response to lung injury would promote orthotopic tumor growth.
To determine whether lung injury promoted growth of orthotopic lung tumors and to study the molecular mechanisms.
We initiated lung injury in C57Bl6 mice using different stimuli, then injected Lewis lung carcinoma cells during the repair phase. We assessed tumor growth 14 days later. We measured tumor angiogenesis, cytokine expression, proliferation, and apoptosis.
Regardless of the mechanism, injured lungs contained more numerous and larger tumors than sham-injured lungs. Tumors from injured lungs were no more vascular, but had higher levels of proliferation and reduced rates of apoptosis. The cytokine macrophage migration inhibitory factor (MIF) was highly expressed in both models of tissue injury. We observed no increase in tumor growth after lung injury in MIF knockout mice. We induced lung-specific overexpression of MIF in a double-transgenic mouse, and observed that MIF overexpression by itself was sufficient to accelerate the growth of orthotopic Lewis lung carcinoma tumors.
Lung injury leads to increased expression of the cytokine MIF, which results in protection from apoptosis and increased proliferation in orthotopic tumors injected after the acute phase of injury.

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Available from: Douglas Arenberg, Jan 03, 2014
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    • "In the specific setting of non-small cell lung cancer (NSCLC), monocyte-derived macrophage secretion of MIF is augmented by NSCLC cells, and secretion of MIF may contribute to local angiogenic activity and tumor metastasis in cell culture models and mouse models of tumor development [11,35-37]. A major breakthrough in our understanding of the role of MIF in tumor metastasis in NSCLC was the identification of CD74 (the invariant chain of the HLA class II peptide) as the cell surface receptor for binding MIF [10,38]. "
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