Expression of Macrophage Migration Inhibitory Factor in Human Breast Cancer: Association with Nodal Spread

Abstract

Macrophage migration inhibitory factor (MIF) is known to exert pleiotropic functions including

Interference of Macrophage Migration Inhibitory Factor Expression in a Mouse Melanoma Inhibits Tumor Establishment by Up-Regulating Thrombospondin-1

“…Similar to our findings in mouse melanoma cells, human melanoma cells were shown to overexpress MIF compared with normal melanocytes (7,8,17,18), and with a MIF antisense plasmid to inhibit MIF expression, tumor cell proliferation was suppressed in vitro (6). Recently, disruption of MIF signaling pathways has been shown to inhibit the growth and invasion of hormone-refractory prostate cancer cells (19).…”

Macrophage migration inhibitory factor (MIF) promotes cell survival by activation of the Akt pathway and role for CSN5/JAB1 in the control of autocrine MIF activity

“…Moreover, the PTEN-siRNA results in HeLa could indicate that, depending on other survival factors, MIF's prosurvival role may be most critical for a tumor cell, when the PI3K/Akt pathway is submaximally activated. Interestingly, it has been suggested that MIF may be particularly important in breast cancers with minimal nodal spread or with a node-negative phenotype and that MIF might play a role in tumor-stroma interactions of primary breast cancers (Bando et al, 2002). In support of such a notion, Hagemann et al (2005) have additionally implicated MIF in macrophageinduced invasiveness of epithelial breast cancer cells .…”

“…At the same time, this system constituted a relevant cancer cell model, as MIF is strongly overexpressed in breast cancer and has been suggested to be associated with breast cancer development (Bando et al, 2002;Hagemann et al, 2005). Our results indicate that enhancement by MIF of Akt phosphorylation and survival is most marked in PTENand p53-negative breast cancer cells, whereas PTEN-and p53-positive breast cancer cells are unresponsive to exogenous MIF with respect to Akt activation and only seem to depend on MIF regarding their survival to a minor extent.…”

“…MIF levels are markedly elevated in numerous tumors such as prostate tumors, breast cancer, melanomas, colon carcinomas and gliomas. MIF promotes cell proliferation and blockade of MIF by antibodies or genetic deletion leads to reduced cellular proliferation and inhibition of tumor growth and angiogenesis (Takahashi et al, 1998;Chesney et al, 1999;Hudson et al, 1999;Shimizu et al, 1999;Mitchell and Bucala, 2000;Bando et al, 2002;Amin et al, 2003;Nishihira et al, 2003). These effects may involve MIF-mediated regulation of CD74-dependent ERK mitogen-activated protein kinase (MAPK) signaling and activation of cytosolic phospholipase A2 (cPLA2) (Mitchell et al, 1999;Leng et al, 2003;Lue et al, 2006), modulation of activities of the tumor-associated protein c-Jun activation domain-binding protein-1 (JAB1) and signaling through the COP9 signalosome (CSN) (Kleemann et al, 2000;Burger-Kentischer et al, 2005).…”

Macrophage Migration Inhibitory Factor: a Potential Marker for Cancer Diagnosis and Therapy

“…Glioblastoma, neuroblastoma, colonic cancer and colorectal cancer have elevated levels of MIF (Shkolnik et al, 1987;Bacher et al, 2003;Ren et al, 2006;Lee et al, 2008). Through ELISA, it was found that the intratumoral level of MIF is indirectly proportional to the tumor involved loco-regional nodes (Bando et al, 2002). In bladder cancer, MIF expression stimulates the proliferation of urothelial tumor cells (Guo et al, 2011).…”