title: Expression of macrophage migration inhibitory factor and CD74 in cervical squamous cell carcinoma.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Obstetrics and Gynecology, The First Hospital of Jilin University, Changchun, Jilin, China.
authors.forename: Rong-Jie
authors.initials: RJ
authors.lastname: Cheng
authors.forename: Wei-Guo
authors.initials: WG
authors.lastname: Deng
authors.forename: Chun-Bo
authors.initials: CB
authors.lastname: Niu
authors.forename: Yi-Yang
authors.initials: YY
authors.lastname: Li
authors.forename: Yan
authors.initials: Y
authors.lastname: Fu
mesh_terms: D000328:Adult; D000368:Aged; D000944:Antigens, Differentiation, B-Lymphocyte / Q000502:physiology; D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D002584:Cervix Uteri / Q000166:cytology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D000949:Histocompatibility Antigens Class II / Q000502:physiology; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000502:physiology; D008263:Macrophage Migration-Inhibitory Factors / Q000502:physiology*; D008875:Middle Aged; D009367:Neoplasm Staging; D002583:Uterine Cervical Neoplasms / Q000473:pathology*; D002578:Uterine Cervical Dysplasia / Q000473:pathology*
chemical_list: D000944:Antigens, Differentiation, B-Lymphocyte; D000949:Histocompatibility Antigens Class II; D008263:Macrophage Migration-Inhibitory Factors; C045084:invariant chain; D019746:Intramolecular Oxidoreductases; C515598:MIF protein, human