Expression of macrophage migration inhibitory factor in human breast cancer: association with nodal spread.
Macrophage migration inhibitory factor (MIF) is known to exert pleiotropic functions including inhibition of macrophage migration, anchoring, and counteraction of the anti-inflammatory and immunosuppressive activity of glucocorticoids. Ninety-three primary breast cancer tissues and 64 sera of primary breast cancer patients were analyzed for the expression of MIF. The clinico-pathological significance of MIF expression was evaluated. It was found that MIF was frequently over-expressed in primary breast cancer tissues. RT-PCR and western blotting analysis confirmed that wild-type MIF is expressed, and immunohistochemical analysis showed that MIF expression was localized at tumor cells as well as stromal cells, including tumor-associated macrophages. Intratumoral MIF protein concentrations detected by enzyme-linked immunosorbent assay (ELISA) varied with a median value of 1821 ng/mg protein (range: 8 - 8126 ng/mg protein), and correlated inversely with nodal involvement (P = 0.039). No significant correlation was observed with other clinico-pathological factors including tumor size, menopausal status and hormone receptors. The circulating level of MIF protein ranged up to 105.7 ng/ml (median: 17.3 ng/ml), and it was also found to correlate inversely with the number of involved nodes (P = 0.02). A comparative study with other soluble inflammatory mediators showed that intratumoral levels of MIF were significantly associated with those of interleukin-1 beta, suggesting that interactions between tumor cells and tumor-associated macrophages play an important role in the up-regulation of MIF. The multifunctional inflammatory/immune mediator MIF was frequently expressed in primary breast cancer, and its expression level was inversely associated with nodal spread. Thus, MIF seems to play a role in tumor-stroma interactions of primary breast cancers, particularly those with a phenotype of node-negative or minimal nodal spread.
Bando
Hiroko
H
Breast Unit, Tokyo Metropolitan Komagome Hospital, Bunkyo-ku, Tokyo 113-0021, Japan.
Matsumoto
Gaku
G
Bando
Masaki
M
Muta
Mariko
M
Ogawa
Taeko
T
Funata
Nobuaki
N
Nishihira
Jun
J
Koike
Morio
M
Toi
Masakazu
M
D000328:Adult; D000368:Aged; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D007150:Immunohistochemistry; D007375:Interleukin-1 / Q000378:metabolism; D008207:Lymphatic Metastasis; D008263:Macrophage Migration-Inhibitory Factors / Q000096:biosynthesis* / Q000235:genetics*; D008264:Macrophages / Q000473:pathology; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic; D010641:Phenotype; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
D007375:Interleukin-1; D008263:Macrophage Migration-Inhibitory Factors