Involvement of macrophage migration inhibitory factor and its receptor (CD74) in human breast cancer
نویسندگان
چکیده
Macrophage migration inhibitory factor (MIF) and its receptor CD74 appear to be involved in tumorigenesis. We evaluated, by immunohistochemical staining, the tissue expression and distribution of MIF and CD74 in serial sections of human invasive breast cancer tumor specimens. The serum MIF level was also determined in breast cancer patients. We showed a significant increase in serum MIF average levels in breast cancer patients compared to healthy individuals. MIF tissue expression, quantified by a modified Allred score, was strongly increased in carcinoma compared to tumor-free specimens, in the cancer cells and in the peritumoral stroma, with fibroblasts the most intensely stained. We did not find any significant correlation with histoprognostic factors, except for a significant inverse correlation between tumor size and MIF stromal positivity. CD74 staining was heterogeneous and significantly decreased in cancer cells but increased in the surrounding stroma, namely in lymphocytes, macrophages and vessel endothelium. There was no significant variation according to classical histoprognostic factors, except that CD74 stromal expression was significantly correlated with triple-negative receptor (TRN) status and the absence of estrogen receptors. In conclusion, our data support the concept of a functional role of MIF in human breast cancer. In addition to auto- and paracrine effects on cancer cells, MIF could contribute to shape the tumor microenvironment leading to immunomodulation and angiogenesis. Interfering with MIF effects in breast tumors in a therapeutic perspective remains an attractive but complex challenge. Level of co-expression of MIF and CD74 could be a surrogate marker for efficacy of anti-angiogenic drugs, particularly in TRN breast cancer tumor.
منابع مشابه
Macrophage migration inhibitory factor involvement in breast cancer (Review)
Macrophage migration inhibitory factor (MIF) is a pleiotropic inflammatory cytokine involved in many cellular processes and in particular carcinogenesis. Here, we review the experimental and clinical published data on MIF and its pathways in breast cancer. Experimental data show that MIF is overexpressed in breast cancer cells (BCC) due, at least partly, to its stabilization by HSP90 and upregu...
متن کاملI-43: Expression Profile of Macrophage Migration Inhibitory Factor (MIF) Signaling Pathway as A Potentional Biomarker in Pathophysiology of Endometriosis
Background MIF via its receptor, CD74, initiates a signaling cascade that leads to proliferation and survival of cells. Also, MIF binding to CD74 activates p38 signaling pathways that lead to positive effect on the expression of COX-2. The aim of this study was to evaluate the gene expression profile of MIF, CD74 and COX-2 in normal, ectopic and eutopic endometrium during menstrual cycle. The e...
متن کاملInhibition of macrophage migration inhibitory factor or its receptor (CD74) attenuates growth and invasion of DU-145 prostate cancer cells.
Macrophage migration inhibitory factor (MIF), a proinflammatory cytokine, is overexpressed in prostate cancer, but the mechanism by which MIF exerts effects on tumor cells remains undetermined. MIF interacts with its identified membrane receptor, CD74, in association with CD44, resulting in ERK 1/2 activation. Therefore, we hypothesized that increased expression or surface localization of CD74 ...
متن کاملSubstance P Increases Cell-Surface Expression of CD74 (Receptor for Macrophage Migration Inhibitory Factor): In Vivo Biotinylation of Urothelial Cell-Surface Proteins
Macrophage migration inhibitory factor (MIF), an inflammatory cytokine, and its receptor CD74 are upregulated by bladder inflammation. MIF-mediated signal transduction involves binding to cell-surface CD74, this study documents, in vivo, MIF-CD74 interactions at the urothelial cell surface. N-hydroxysulfosuccinimide biotin ester-labeled surface urothelial proteins in rats treated either with sa...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
دوره 32 شماره
صفحات -
تاریخ انتشار 2014