Further evidence for increased macrophage migration inhibitory factor expression in prostate cancer. BMC Cancer 2005 Jul 06;5:73
Date
07/08/2005Pubmed ID
16000172Pubmed Central ID
PMC1177932DOI
10.1186/1471-2407-5-73Scopus ID
2-s2.0-26844433956 (requires institutional sign-in at Scopus site) 62 CitationsAbstract
BACKGROUND: Macrophage migration inhibitory factor (MIF) is a cytokine associated with prostate cancer, based on histologic evidence and circulating (serum) levels. Recent studies from another laboratory failed to document these results. This study's aims were to extend and confirm our previous data, as well as to define possible mechanisms for the discrepant results. Additional aims were to examine MIF expression, as well as the location of MIF's receptor, CD74, in human prostatic adenocarcinoma compared to matched benign prostate.
METHODS: MIF amounts were determined in random serum samples remaining following routine PSA screening by ELISA. Native, denaturing and reducing polyacrylamide gels and Western blot analyses determined the MIF form in serum. Prostate tissue arrays were processed for MIF in situ hybridization and immunohistochemistry for MIF and CD74. MIF released into culture medium from normal epithelial, LNCaP and PC-3 cells was detected by Western blot analysis.
RESULTS: Median serum MIF amounts were significantly elevated in prostate cancer patients (5.87 +/- 3.91 ng/ml; +/- interquartile range; n = 115) compared with patients with no documented diagnosis of prostate cancer (2.19 +/- 2.65 ng/ml; n = 158). ELISA diluent reagents that included bovine serum albumin (BSA) significantly reduced MIF serum detection (p < 0.01). MIF mRNA was localized to prostatic epithelium in all samples, but cancer showed statistically greater MIF expression. MIF and its receptor (CD74) were localized to prostatic epithelium. Increased secreted MIF was detected in culture medium from prostate cancer cell lines (LNCaP and PC-3).
CONCLUSION: Increased serum MIF was associated with prostate cancer. Diluent reagents that included BSA resulted in MIF serum immunoassay interference. In addition, significant amounts of complexed MIF (180 kDa under denaturing conditions by Western blot) found in the serum do not bind to the MIF capture antibody. Increased MIF mRNA expression was observed in prostatic adenocarcinoma compared to benign tissue from matched samples, supporting our earlier finding of increased MIF gene expression in prostate cancer.
Author List
Meyer-Siegler KL, Iczkowski KA, Vera PLMESH terms used to index this publication - Major topics in bold
AdenocarcinomaAntigens, Differentiation, B-Lymphocyte
Blotting, Western
Cell Line, Tumor
Enzyme-Linked Immunosorbent Assay
Epithelium
Gene Expression Regulation, Neoplastic
Histocompatibility Antigens Class II
Humans
Immunohistochemistry
Immunoprecipitation
In Situ Hybridization
Macrophage Migration-Inhibitory Factors
Male
Prostate
Prostate-Specific Antigen
Prostatic Neoplasms
RNA, Messenger
Serum Albumin, Bovine
