RT Journal Article
SR Electronic
T1 Expression of Macrophage Migration Inhibitory Factor and CD74 in Cervical Squamous Cell Carcinoma
JF International Journal of Gynecologic Cancer
JO Int J Gynecol Cancer
FD BMJ Publishing Group Ltd
SP 1004
OP 1012
DO 10.1097/IGC.0b013e31821c45b7
VO 21
IS 6
A1 Rong-jie Cheng
A1 Wei-guo Deng
A1 Chun-bo Niu
A1 Yi-yang Li
A1 Yan Fu
YR 2011
UL http://ijgc.bmj.com/content/21/6/1004.abstract
AB Objective: Macrophage migration inhibitory factor (MIF) and CD74 emerge as important players in pathogenesis and angiogenesis of several types of malignant tumors. The purpose of this study was to evaluate the expression of MIF and CD74 in cervical squamous cell carcinoma and explore the potential roles they play in cervical tumor angiogenesis.Methods: Macrophage migration inhibitory factor and CD74 expression was assessed by immunohistochemistry in 209 cases with various degrees of cervical epithelial lesions, including 40 normal cervical epithelia, 43 mild cervical intraepithelial neoplasia 1 (CIN 1), 41 moderate-severe cervical intraepithelial neoplasia (CIN 2 to 3), and 85 cervical squamous cell carcinomas (SCCs). CD34 staining was used for counting microvessel density. Semiquantitative reverse transcription polymerase chain reaction and Western blot were used to detect messenger RNA and protein levels of MIF and CD74 in normal and malignant cervical tissues and cervical cancer cell lines SiHa and C-33A. The concentration of vascular endothelial growth factor (VEGF) in the conditioned media of cervical cancer cells was analyzed by enzyme-linked immunosorbent assay.Results: Immunohistochemical analysis showed that MIF and CD74 expression was significantly higher in CIN than in the normal samples and higher in SCC than in CIN. The overexpression of MIF was correlated with deep stromal infiltration but not with the other clinicopathologic features of SCC. Correlation analyses revealed that MIF was positively related to CD74, and both protein levels were associated with microvessel density. Exogenous MIF induced VEGF secretion in SiHa and C-33A cells in a dose-dependent manner, which can be inhibited by MIF-specific inhibitor (ISO-1) or anti-CD74 antibody.Conclusion: Overexpression of MIF and CD74 in SCC and its precancerous lesions and the up-regulation of VEGF secretion in cervical cancer cells indicate that MIF and CD74 may play critical roles in the pathogenesis and angiogenesis of cervical cancer.