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Originally published online as doi:10.2353/ajpath.2009.080463 on January 8, 2009

Published online before print January 8, 2009
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(American Journal of Pathology. 2009;174:638-646.)
© 2009 American Society for Investigative Pathology
DOI: 10.2353/ajpath.2009.080463

Expression of CD74, the Receptor for Macrophage Migration Inhibitory Factor, in Non-Small Cell Lung Cancer

Marc McClelland, Liujian Zhao, Shannon Carskadon and Douglas Arenberg

From the Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, University of Michigan Medical Center, Ann Arbor, Michigan

Macrophage migration inhibitory factor (MIF) is a multifunctional cytokine that is overexpressed in lung cancer. The MIF receptor was recently discovered and found to be the invariant chain of the HLA class II molecule, CD74. We hypothesized that the expression of this receptor-ligand pair in lung cancer is associated with the angiogenic activity and level of CXC chemokine expression in human specimens of non-small cell lung cancer. We, therefore, performed immunolocalization of CD74 and compared it with the localization of MIF in non-small cell lung cancer to determine their respective locations, as well as the relationship between the co-expression of MIF-CD74 and angiogenic CXC chemokines with tumor angiogenesis. We found intense CD74 expression by immunohistochemistry in 57 of 70 tumors with minimal to no staining in the remaining 13 tumors. Comparing the localization of CD74 with its putative ligand, MIF, we found that CD74 and MIF were co-expressed in tumors in close proximity, and that co-expression of the MIF-CD74 pair was associated with both higher levels of tumor-associated angiogenic CXC chemokines (ie, the ELR score) and greater vascularity compared with tumors in which MIF-CD74 co-expression was not present. We also found that MIF induced angiogenic CXC chemokine expression in an autocrine manner in vitro, a function that was specifically inhibited by antibodies to CD74.






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Copyright © 2009 by the American Society for Investigative Pathology.