Role of macrophage migration inhibitory factor in primary glioblastoma multiforme cells

Baron, Nina; Deuster, Oliver; Noelker, Carmen; Stüer, Carsten; Strik, Herwig; Schaller, Carlo; Dodel, Richard; Meyer, Bernhard; Bacher, Michael

doi:10.1002/jnr.22595

Cited by 39 publications

(31 citation statements)

References 61 publications

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“…Furthermore, our data confirmed worst prognosis for high-grade glioblastoma with high levels of CD74 expression. However, our data suggest that CD74 expression alone is not an independent marker for poor prognosis and it requires the expression of MIF for tumor pathogenesis, as previously reported in other studies (4,7,16,17,18) . Although we did not perform co-localization staining for MIF-CD74 in this retrospective study, evidence of MIF and CD74 co-localization reported in several other studies (7,8,9,10,11,12,13,14) .…”

Section: Discussionsupporting

confidence: 77%

“…In line with this observation, we demonstrated overexpression of MIF in grade II-IV astrocytoma, and that overexpression of CD74 is associated with tumor progression in astrocytoma at the gene and transcription levels. MIF exerts multimodal functions in glioblastoma including pro-proliferative, promigratory, pro-angiogenic as well as immune-evasive properties through CD74 (16,17,18) . The binding of MIF to the extracellular domain of CD74 is necessary as an initial step in the MIF signaling cascade (4) resulting in tumor vascularization and the promotion of neoplastic Fig.…”

Section: Discussionmentioning

confidence: 99%

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CD74 as a Potential Prognostic Marker in Glioblastoma

Narsia

Ramagiri

Lomtadze³

et al. 2017

IAM

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CD74 is a cell membrane receptor for macrophage migration inhibitory factor (MIF) that is believed to play a role in tumor progression and metastasis. Astrocytoma is the most common type of brain cancers, which are classified by the World Health Organization (WHO) into four grades according to the degree of malignancy. In this study, we investigated MIF and CD74 gene expression levels in a large cohort of publicly available RNA sequencing data and evaluated the correlation between their protein expression with clinicopathological features as well as prognosis in an independent cohort of astrocytoma samples. Seventy-three patients with different grades of astrocytoma (WHO grade II diffuse astrocytoma, grade III anaplastic astrocytoma, and grade IV glioblastoma) were used for protein expression in this study. The expression of CD74 was assayed by immunohistochemistry and was significantly higher in highgrade glioblastoma than grade II and grade III astrocytoma (P < 0.004). Upregulated CD74 expression was frequently found in older patients (≥ 62 years). The expression of CD74 is correlated with overall survival (P = 0.05). Multivariate analysis shows that the CD74 expression is associated with poor prognosis in the presence of MIF expression (P = 0.039) and that CD74 is not an independent prognostic marker in glioblastoma. However, similar studies on larger sample size are required to make a definite conclusion on the role of CD74 in prognosis in glioblastoma.

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Section: Discussionsupporting

confidence: 77%

Section: Discussionmentioning

confidence: 99%

CD74 as a Potential Prognostic Marker in Glioblastoma

Narsia

Ramagiri

Lomtadze³

et al. 2017

IAM

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“…MIF expression in GBM has been previously reported [51, 52], but its role in GBM-mediated immunosuppression is only beginning to be elucidated [53]. However, in other tumors MIF secretion is associated with increased intratumoral mMDSCs [54] and adding an inhibitor of MIF’s keto-enol tautomerase activity to tumor supernatant has decreased the formation of mMDSCs.…”

Section: Discussionmentioning

confidence: 99%

Modulating glioma-mediated myeloid-derived suppressor cell development with sulforaphane

et al. 2017

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Glioblastoma is the most common primary tumor of the brain and has few long-term survivors. The local and systemic immunosuppressive environment created by glioblastoma allows it to evade immunosurveillance. Myeloid-derived suppressor cells (MDSCs) are a critical component of this immunosuppression. Understanding mechanisms of MDSC formation and function are key to developing effective immunotherapies. In this study, we developed a novel model to reliably generate human MDSCs from healthy-donor CD14+ monocytes by culture in human glioma-conditioned media. Monocytic MDSC frequency was assessed by flow cytometry and confocal microscopy. The resulting MDSCs robustly inhibited T cell proliferation. A cytokine array identified multiple components of the GCM potentially contributing to MDSC generation, including Monocyte Chemoattractive Protein-1, interleukin-6, interleukin-8, and Macrophage Migration Inhibitory Factor (MIF). Of these, Macrophage Migration Inhibitory Factor is a particularly attractive therapeutic target as sulforaphane, a naturally occurring MIF inhibitor derived from broccoli sprouts, has excellent oral bioavailability. Sulforaphane inhibits the transformation of normal monocytes to MDSCs by glioma-conditioned media in vitro at pharmacologically relevant concentrations that are non-toxic to normal leukocytes. This is associated with a corresponding increase in mature dendritic cells. Interestingly, sulforaphane treatment had similar pro-inflammatory effects on normal monocytes in fresh media but specifically increased immature dendritic cells. Thus, we have used a simple in vitro model system to identify a novel contributor to glioblastoma immunosuppression for which a natural inhibitor exists that increases mature dendritic cell development at the expense of myeloid-derived suppressor cells when normal monocytes are exposed to glioma conditioned media.

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“…For example, in a previous study, a BrdU assay revealed that in glioblastoma cell lines treated with isoxazoline (ISO)-1, cell proliferation was inhibited in a concentration-dependent manner (42). Similarly, the use of MIF or CD74 neutralizing antibodies has been demonstrated to inhibit human prostate cancer cell (DU-145) proliferation (14).…”

Section: Mif and Cell Proliferation Shi Et Almentioning

confidence: 97%

Involvement of macrophage migration inhibitory factor in cancer and novel therapeutic targets

et al. 2016

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Abstract. Macrophage migration inhibitory factor (MIF) was originally identified in 1966 by Bloom and Bennett as a pro-inflammatory cytokine involved in the inhibition of macrophage motility. Since then, studies have investigated the functional contribution of this pro-inflammatory cytokine in several immune diseases, including rheumatoid arthritis and lupus erythematous. Recently, MIF has been reported to be involved in a variety of neoplastic diseases. The present review discusses previous cancer research studies that have investigated the involvement of MIF in carcinogenesis, disease prognosis, tumor cell proliferation and invasion, and tumor-induced angiogenesis. Finally, potential therapeutic approaches based on the use of MIF antagonists and neutralizing antibodies are examined. The review concludes that MIF could be a good prognostic biomarker in several types of cancer, but also that the inhibition of MIF could represent a novel therapy against cancer.

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Role of macrophage migration inhibitory factor in primary glioblastoma multiforme cells

Cited by 39 publications

References 61 publications

CD74 as a Potential Prognostic Marker in Glioblastoma

CD74 as a Potential Prognostic Marker in Glioblastoma

Modulating glioma-mediated myeloid-derived suppressor cell development with sulforaphane

Involvement of macrophage migration inhibitory factor in cancer and novel therapeutic targets

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