Macrophage Inhibitory Cytokine-1 Is Overexpressed in Malignant Melanoma and Is Associated with Tumorigenicity

Boyle, Glen M.; Pedley, Julie; Martyn, A.; Banducci, Kelly J.; Strutton, Geoffrey; Brown, David A.; Breit, Samuel N.; Parsons, Peter G.

doi:10.1038/jid.2008.270

Cited by 98 publications

(112 citation statements)

References 48 publications

(59 reference statements)

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“…Additionally, GDF15 is known to promote apoptosis in colorectal tumor cells [27] and induces apoptosis in breast [28] and prostate cancer cell lines [25]. However, GDF15 has also been implicated in the progression and metastasis of malignant melanoma [29], consistent with our findings in the breast cancer model. Collectively, these studies indicate that the role and effect of GDF15 may be different depending on the cell type, stage, and extent of the tumor producing it and perhaps its secreted form, as has been found for other members of the TGF-b superfamily.…”

Section: Discussionsupporting

confidence: 82%

Role of GDF15 in radiosensitivity of breast cancer cells

et al. 2014

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The Growth Differentiation Factor-15 gene (GDF15) is a member of TGF-b superfamily and this cytokine family is considered to be a promising target for cancer therapy. The purpose of this study was to investigate the effect of tumor derived GDF15 on proliferation and radiosensitivity of breast cancer cells in vitro and in vivo. A mouse breast cancer LM2 cell line with stable transfection of full-length mouse GDF15 cDNA was established. Cell growth and proliferation was observed using WST assay and impedance-based method. Radiation induced GDF15 and TGF-b1 expression was determined by qRT-PCR. Radiosensitivity was measured by a colony formation assay in vitro and by a tumor growth delay assay in vivo. Cells with more than a 10-fold increase in GDF15 expression had a higher growth rate than parental control cells in vitro and in vivo. The radiation induced elevation of the expression of TGFb1 was reduced in GDF15 overexpressing cells. GDF15 may play a role in the radiation response of breast cancer cells by effecting cell survival, inhibiting radiation-induced cell death, and inhibiting the TGF-b1 related cytotoxic action.

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Section: Discussionsupporting

confidence: 82%

Role of GDF15 in radiosensitivity of breast cancer cells

et al. 2014

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“…Interestingly, impairing GDF-15 can inhibit viral replication. 70 In malignant melanomas, GDF-15 is highly overexpressed, 71 and it is able to mimic VEGF in the neovascularization in the tumor site. 72 Similarly, in malignant glioblastomas, GDF-15 is upregulated as a reaction to anoxia, suggesting more general involvement in vascularization development.…”

Section: Gdf-15 In Cancer Progression Systemic and Immune Responsementioning

confidence: 99%

Growth/differentiation factor-15: prostate cancer suppressor or promoter?

Vaňhara

Hampl

Kozubı́k

et al. 2012

Prostate Cancer Prostatic Dis

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Deregulation of expression and function of cytokines belonging to the transforming growth factor-b (TGF-b) family is often associated with various pathologies. For example, this cytokine family has been considered a promising target for cancer therapy. However, the detailed functions of several cytokines from the TGF-b family that could have a role in cancer progression and therapy remain unclear. One of these molecules is growth/differentiation factor-15 (GDF-15), a divergent member of the TGF-b family. This stress-induced cytokine has been proposed to possess immunomodulatory functions and its high expression is often associated with cancer progression, including prostate cancer (PCa). However, studies clearly demonstrating the mechanisms for signal transduction and functions in cell interaction, cancer progression and therapy are still lacking. New GDF-15 roles have recently been identified for modulating osteoclast differentiation and for therapy for PCa bone metastases. Moreover, GDF-15 is as an abundant cytokine in seminal plasma with immunosuppressive properties. We discuss studies that focus on the regulation of GDF-15 expression and its role in tissue homeostasis, repair and the immune response with an emphasis on the role in PCa development.

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“…MIC-1 is not expressed in most human tissues at basal conditions (except the placenta) but is expressed at high concentrations during inflammation and injury (Fairlie et al, 1999;Schober et al, 2001). MIC-1 is overexpressed by malignant melanoma cells and is associated with tumourigenicity (Boyle et al, 2009). High serum concentrations of MIC-1 have been observed in patients with pancreatic (Koopmann et al, 2004(Koopmann et al, , 2006, gastric (Baek et al, 2009), and breast cancer (Welsh et al, 2003), and have been associated with adverse survival in colorectal cancer and glioblastoma (Shnaper et al, 2009).…”

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confidence: 99%

Plasma MIC-1 correlates with systemic inflammation but is not an independent determinant of nutritional status or survival in oesophago-gastric cancer

et al. 2010

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BACKGROUND: Macrophage inhibitory cytokine-1(MIC-1) is a potential modulator of systemic inflammation and nutritional depletion, both of which are adverse prognostic factors in oesophago-gastric cancer (OGC). METHODS: Plasma MIC-1, systemic inflammation (defined as plasma C-reactive protein (CRP) of X10 mg l -1 or modified Glasgow prognostic score (mGPS) of X1), and nutritional status were assessed in newly diagnosed OGC patients (n ¼ 293). Healthy volunteers (n ¼ 35) served as controls. RESULTS: MIC-1 was elevated in patients (median ¼ 1371 pg ml -1 ; range 141 -39 053) when compared with controls (median ¼ 377 pg ml -1 ; range 141 -3786; Po0.001). Patients with gastric tumours (median ¼ 1592 pg ml -1 ; range 141 -12 643) showed higher MIC-1 concentrations than patients with junctional (median ¼ 1337 pg ml -1 ; range 383 -39 053) and oesophageal tumours (median ¼ 1180 pg ml -1 ; range 258 -31 184; P ¼ 0.015). Patients showed a median weight loss of 6.4% (range 0.0 -33.4%), and 42% of patients had an mGPS of X1 or plasma CRP of X10 mg l -1 (median ¼ 9 mg l -1 ; range 1 -200). MIC-1 correlated positively with disease stage (r 2 ¼ 0.217; Po0.001), age (r 2 ¼ 0.332; Po0.001), CRP (r 2 ¼ 0.314; Po0.001), and mGPS (r 2 ¼ 0.336; Po0.001), and negatively with Karnofsky Performance Score (r 2 ¼ À0.269; Po0.001). However, although MIC-1 correlated weakly with dietary intake (r 2 ¼ 0.157; P ¼ 0.031), it did not correlate with weight loss, BMI, or anthropometry. Patients with MIC-1 levels in the upper quartile showed reduced survival (median ¼ 204 days; 95% CI 157 -251) when compared with patients with MIC-1 levels in the lower three quartiles (median ¼ 316 days; 95% CI 259 -373; P ¼ 0.036), but MIC-1 was not an independent prognostic indicator. CONCLUSIONS: There is no independent link between plasma MIC-1 levels and depleted nutritional status or survival in OGC.

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Macrophage Inhibitory Cytokine-1 Is Overexpressed in Malignant Melanoma and Is Associated with Tumorigenicity

Cited by 98 publications

References 48 publications

Role of GDF15 in radiosensitivity of breast cancer cells

Role of GDF15 in radiosensitivity of breast cancer cells

Growth/differentiation factor-15: prostate cancer suppressor or promoter?

Plasma MIC-1 correlates with systemic inflammation but is not an independent determinant of nutritional status or survival in oesophago-gastric cancer

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