Macrophage migration inhibitory factor and CXC chemokine expression in non-small cell lung cancer: role in angiogenesis and prognosis.
OBJECTIVE
The purpose of this study was to determine whether expression of migration inhibitory factor (MIF) is increased in non-small cell lung cancer, and whether it correlates with angiogenesis and/or prognosis.


METHODS
We measured vessel density, and levels of MIF, angiogenic CXC chemokines, and vascular-endothelial growth factor (VEGF; by ELISA) in tumor and normal lung tissue from 87 patients after resection of lung cancer. We compared vessel density with levels of MIF, VEGF, or angiogenic CXC chemokines in the corresponding tumor homogenate. Disease-free survival was analyzed in a Cox proportional hazards model.


RESULTS
Levels of MIF in lung cancer demonstrated a bimodal distribution, with some having "normal" values (relative to normal lung tissue) and a second cluster with markedly high values. The increased levels of MIF in lung cancer were statistically significant in both paired and unpaired comparisons (P < 0.05). The strongest correlation of vessel density was with the sum of angiogenic CXC chemokines. MIF correlated very strongly with levels of angiogenic CXC chemokines. Tumors in the high MIF group had a strong correlation between MIF level and vessel density. Risk of recurrence was associated with high levels of glutamic acid-leucine-arginine amino acid motif CXC chemokines, MIF, and/or VEGF in a Cox proportional hazards model.


CONCLUSIONS
MIF expression in non-small cell lung cancer occurs in a bimodal distribution, and is closely associated with tumor levels of angiogenic CXC chemokines and with vessel density. High levels of tumor-associated CXC chemokines, MIF, or VEGF are associated with risk of recurrence after resection of lung cancer.
White
Eric S
ES
Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, University Of Michigan Medical Center, Ann Arbor, Michigan 48109-0642, USA.
Flaherty
Kevin R
KR
Carskadon
Shannon
S
Brant
Ashley
A
Iannettoni
Mark D
MD
Yee
John
J
Orringer
Mark B
MB
Arenberg
Douglas A
DA
D002289:Carcinoma, Non-Small-Cell Lung / Q000098:blood supply / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D019743:Chemokines, CXC / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007150:Immunohistochemistry; D008168:Lung / Q000276:immunology; D008175:Lung Neoplasms / Q000098:blood supply / Q000276:immunology* / Q000473:pathology / Q000601:surgery; D008263:Macrophage Migration-Inhibitory Factors / Q000378:metabolism*; D009389:Neovascularization, Pathologic / Q000276:immunology*; D012008:Recurrence; D012016:Reference Values
D019743:Chemokines, CXC; D008263:Macrophage Migration-Inhibitory Factors