OBJECTIVE: The objectives of this study were: 1) to examine the expression of macrophage migration inhibitory factor (MIF) in esophageal squamous cell carcinoma (ESCC); 2) to see if a relationship exists between MIF expression, clinicopathologic features, and long-term prognosis; and 3) to ascertain the possible biologic function of MIF in angiogenesis. SUMMARY BACKGROUND DATA: MIF has been linked to fundamental processes such as those controlling cell proliferation, cell survival, angiogenesis, and tumor progression. Its role in ESCC, and the correlation of MIF expression and tumor pathologic features in patients, has not been elucidated. METHODS: The expression of MIF in tumor and nontumor tissues was examined by immunohistochemical staining. Concentrations of MIF, vascular endothelial growth factor (VEGF), and interleukin-8 (IL-8) in patients' sera and in the supernatant of tumor cells culture were examined by ELISA. Correlations with clinicopathologic factors were made. RESULTS: In 72 patients with ESCC, intracellular MIF was overexpressed in esophagectomy specimens. The expression of MIF correlated with both tumor differentiation and lymph node status. The median survival in the low-MIF expression group (<50% positively stained cancer cells on immunohistochemistry) and high expression group (>/=50% positively stained cancer cells) was 28.3 months and 15.8 months, respectively (P = 0.03). The 3-year survival rates for the 2 groups were 37.7% and 12.1%, respectively. MIF expression was related to microvessel density; increased MIF serum levels also correlated with higher serum levels of VEGF. In addition, in vitro MIF stimulation of esophageal cancer cell lines induced a dose-dependent increase in VEGF and IL-8 secretion. CONCLUSIONS: These results demonstrate, for the first time, that human esophageal carcinomas express and secrete large amounts of MIF. Through its effects on VEGF and IL-8, MIF may serve as an autocrine factor in angiogenesis and thus play an important role in the pathogenesis of ESCC.
OBJECTIVE: The objectives of this study were: 1) to examine the expression of macrophage migration inhibitory factor (MIF) in esophageal squamous cell carcinoma (ESCC); 2) to see if a relationship exists between MIF expression, clinicopathologic features, and long-term prognosis; and 3) to ascertain the possible biologic function of MIF in angiogenesis. SUMMARY BACKGROUND DATA: MIF has been linked to fundamental processes such as those controlling cell proliferation, cell survival, angiogenesis, and tumor progression. Its role in ESCC, and the correlation of MIF expression and tumor pathologic features in patients, has not been elucidated. METHODS: The expression of MIF in tumor and nontumor tissues was examined by immunohistochemical staining. Concentrations of MIF, vascular endothelial growth factor (VEGF), and interleukin-8 (IL-8) in patients' sera and in the supernatant of tumor cells culture were examined by ELISA. Correlations with clinicopathologic factors were made. RESULTS: In 72 patients with ESCC, intracellular MIF was overexpressed in esophagectomy specimens. The expression of MIF correlated with both tumor differentiation and lymph node status. The median survival in the low-MIF expression group (<50% positively stained cancer cells on immunohistochemistry) and high expression group (>/=50% positively stained cancer cells) was 28.3 months and 15.8 months, respectively (P = 0.03). The 3-year survival rates for the 2 groups were 37.7% and 12.1%, respectively. MIF expression was related to microvessel density; increased MIF serum levels also correlated with higher serum levels of VEGF. In addition, in vitro MIF stimulation of esophageal cancer cell lines induced a dose-dependent increase in VEGF and IL-8 secretion. CONCLUSIONS: These results demonstrate, for the first time, that humanesophageal carcinomas express and secrete large amounts of MIF. Through its effects on VEGF and IL-8, MIF may serve as an autocrine factor in angiogenesis and thus play an important role in the pathogenesis of ESCC.
Authors: H Y Lan; N Yang; F G Brown; N M Isbel; D J Nikolic-Paterson; W Mu; C N Metz; M Bacher; R C Atkins; R Bucala Journal: Transplantation Date: 1998-12-15 Impact factor: 4.939
Authors: L Bini; B Magi; B Marzocchi; F Arcuri; S Tripodi; M Cintorino; J C Sanchez; S Frutiger; G Hughes; V Pallini; D F Hochstrasser; P Tosi Journal: Electrophoresis Date: 1997-12 Impact factor: 3.535
Authors: J Bernhagen; T Calandra; R A Mitchell; S B Martin; K J Tracey; W Voelter; K R Manogue; A Cerami; R Bucala Journal: Nature Date: 1993-10-21 Impact factor: 49.962
Authors: Millicent Winner; Albert C Koong; Beatriz E Rendon; Wayne Zundel; Robert A Mitchell Journal: Cancer Res Date: 2007-01-01 Impact factor: 12.701
Authors: Nadège Kindt; Julie Preillon; Herbert Kaltner; Hans-Joachim Gabius; Dominique Chevalier; Alexandra Rodriguez; Bryon D Johnson; Véronique Megalizzi; Christine Decaestecker; Guy Laurent; Sven Saussez Journal: J Cancer Res Clin Oncol Date: 2013-01-25 Impact factor: 4.553