Overexpression of macrophage migration inhibitory factor induces angiogenesis and deteriorates prognosis after radical resection for hepatocellular carcinoma

Autor: Osama N. El-Assal, Akira Yamanoi, Takashi Ono, Dipok Kumar Dhar, Naofumi Nagasue, Yoshitaka Hishikawa, Eiji Hira
Rok vydání: 2005
Předmět:
Male
Cancer Research
Pathology
medicine.medical_specialty
Carcinoma
Hepatocellular
Angiogenesis
animal diseases
medicine.medical_treatment
Blotting
Western
Antigens
CD34
chemical and pharmacologic phenomena
Disease-Free Survival
Neovascularization
Predictive Value of Tests
Biomarkers
Tumor
Tumor Cells
Cultured
otorhinolaryngologic diseases
Carcinoma
medicine
Hepatectomy
Humans
Macrophage Migration-Inhibitory Factors
Aged
Tube formation
Neovascularization
Pathologic
business.industry
Liver Neoplasms
Cancer
Middle Aged
Prognosis
medicine.disease
Immunohistochemistry
biological factors
digestive system diseases
Up-Regulation
Gene Expression Regulation
Neoplastic
Cytokine
Oncology
Multivariate Analysis
Cancer research
Female
Macrophage migration inhibitory factor
alpha-Fetoproteins
medicine.symptom
business
Zdroj: Cancer. 103:588-598
ISSN: 1097-0142
0008-543X
DOI: 10.1002/cncr.20818
Popis: BACKGROUND Macrophage migration inhibitory factor (MIF) is a pivotal cytokine that regulates inflammatory and immune responses. Recently, many investigators reported that MIF is expressed highly in several tumors, including hepatocellular carcinoma (HCC). However, the role of MIF in tumor angiogenesis and patient prognosis has not been examined in patients with HCC. METHODS The authors evaluated MIF expression in 56 samples of HCC by Western blot analysis, and the results were correlated with clinicopathologic factors and patient prognosis. MIF localization was determined by immunohistochemical methods, and the results were compared with tumor microvessel density (MVD), as assessed by anti-CD34 antibody. Furthermore, to validate the role of MIF in angiogenesis, both MIF expression during culture of HCC cells (using the Hep3B, HepG2, and Huh7 cell lines) under hypoxic condition and the angiogenic potential of recombinant MIF in an in vitro angiogenic model were examined. RESULTS Tumors with high MIF expression had high α-fetoprotein levels (P = 0.049) and frequent intrahepatic recurrence (P = 0.043). Immunohistochemical MIF scores had a significant correlation with MVD (P = 0.007). Patients who had tumors with high MIF expression levels had a significantly worse (P = 0.025) disease-free survival, and this finding remained significant as an independent prognostic factor in the multivariate analysis. Hep3B cells had high expression of MIF at 6 hours and 12 hours after hypoxic stress and exogenous MIF stimulated endothelial tube formation in in vitro angiogenesis. CONCLUSIONS The current findings suggest that MIF expression may play a pivotal role in the dismal prognosis of patients with HCC that may be attributable to the modulation of angiogenesis. Cancer 2005. © 2004 American Cancer Society.
Databáze: OpenAIRE
Externí odkaz: