Interferon-α Sensitivity in Melanoma Cells: Detection of Potential Response Marker Genes

Certa, Ulrich; Seiler, Monika; Padovan, Elisabetta; Spagnoli, Giulio C.

doi:10.1007/978-3-642-59410-6_12

Cited by 11 publications

(7 citation statements)

References 19 publications

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“…20 These results are in line with published data showing reduced expression of MLANA, TRP-1, tyrosinase and gp100 in melanoma cells incubated with IFN-c or TNF-a 21,22 and the absence of effect with IFNa. 23 We sought to extend our study to another inflammatory cytokine, namely IL-1. There are three founding members of the IL-1 gene family, two of which are agonists, IL-1a and IL-1b, and the third is IL-1 receptor antagonist (IL-1Ra; reviewed in Ref.…”

Section: Resultsmentioning

confidence: 99%

Interleukins 1α and 1β secreted by some melanoma cell lines strongly reduce expression of MITF‐M and melanocyte differentiation antigens

Kholmanskikh

Baren

Brasseur

et al. 2010

Intl Journal of Cancer

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We report that melanoma cell lines expressing the interleukin-1 receptor exhibit 4-to 10-fold lower levels of mRNA of microphthalmia-associated transcription factor (MITF-M) when treated with interleukin-1b. This effect is NF-jB and JNKdependent. MITF-M regulates the expression of melanocyte differentiation genes such as MLANA, tyrosinase and gp100, which encode antigens recognized on melanoma cells by autologous cytolytic T lymphocytes. Accordingly, treating some melanoma cells with IL-1b reduced by 40-100% their ability to activate such antimelanoma cytolytic T lymphocytes. Finally, we observed large amounts of biologically active IL-1a or IL-1b secreted by two melanoma cell lines that did not express MITF-M, suggesting an autocrine MITF-M downregulation. We estimate that~13% of melanoma cell lines are MITF-M-negative and secrete IL-1 cytokines. These results indicate that the repression of melanocyte-differentiation genes by IL-1 produced by stromal cells or by tumor cells themselves may represent an additional mechanism of melanoma immune escape.

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Section: Resultsmentioning

confidence: 99%

Interleukins 1α and 1β secreted by some melanoma cell lines strongly reduce expression of MITF‐M and melanocyte differentiation antigens

Kholmanskikh

Baren

Brasseur

et al. 2010

Intl Journal of Cancer

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“…Therefore, an influence of the inflammatory micromilieu in RA-ST on the H19 RNA expression in SFBs is unlikely, although recent studies have demonstrated the regulation of H19 expression by hepatocyte growth factor in epithelial cells 52 or by interferon-␣ in melanoma cells. 53 In both RA-and OA-SFBs, the H19 expression in serum-starved and IL-1␤-or PDGF-stimulated cells was significantly altered by inhibitors of the MAP-kinases ERK-1/2 and the phosphatidylinositol-3 kinase ( Figure 6). This is in agreement with the inhibition of hepatocyte growth factor-induced H19 expression by MAP-kinase inhibitors in epithelial cells 52 and underlines the importance of these two signal transduction pathways for H19 promoter transactivation.…”

Section: Discussionmentioning

confidence: 98%

Detection of Oncofetal H19 RNA in Rheumatoid Arthritis Synovial Tissue

Stuhlmüller

Kunisch

Franz

et al. 2003

The American Journal of Pathology

104

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The expression of oncofetal H19 RNA and its localization/cellular source was analyzed in synovial tissue (ST) and isolated synovial macrophages (Mphi) or synovial fibroblasts (SFBs) by reverse transcriptase-polymerase chain reaction (RT-PCR), in situ hybridization, and immunohistochemistry. RT-PCR showed significantly higher H19 expression in ST from patients with rheumatoid arthritis (RA) (P = 0.000) and osteoarthritis (OA) (P = 0.009) than in normal/joint trauma controls (N/JT), but comparable levels in reactive arthritis. In situ hybridization demonstrated strong signals in all RA-ST samples (n = 8), with > or =85% positive cells in the lining layer, diffuse infiltrates, and stroma regions. In lymphoid aggregates and endothelial cells only 20% were positive. RA-ST contained a significantly higher percentage of strongly positive lining cells than OA-ST and N/JT-ST. H19 RNA was expressed in both Mphi and SFBs, as confirmed by RT-PCR in isolated RA Mphi and SFBs (n = 3). In RA-SFBs, low constitutive H19 RNA expression in culture (10% fetal calf serum) was strongly increased on starvation (3.5-fold, 1% fetal calf serum), with or without the addition of interleukin-1beta (10 to 100 U/ml), tumor necrosis factor-alpha (1 to 25 ng/ml), or platelet-derived growth factor-BB (2.5 to 10 U/ml). In OA-SFBs, this starvation-induced increase was lower (twofold), reaching significant differences compared with RA-SFBs after stimulation with interleukin-1beta and platelet-derived growth factor-BB. In both RA- and OA-SFBs, the MAP-kinase ERK-1/2 pathway and the phosphatidylinositol-3 kinase pathway influenced H19 RNA expression, as shown by inhibitor studies. Significant overexpression of H19 RNA and its increased sensitivity to starvation/cytokine regulation in RA suggests a pathogenetic role of this oncofetal gene, possibly reflecting embryonal dedifferentiation of the adult ST and/or ongoing inflammatory/oxidative stress.

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“…The possible existence of an interconnection among cutaneous melanoma and imprinted genes, in special the IGF2 and H19 genes, is an open question urging for answer, since some authors have shown H19 and IGF2 differential expression (or of genes and proteins related to the protein IGF-II, such as IG2R and IMP-3) in melanoma [8][9][10][11][12][13]. Although these studies may indicate an important role of the IGF2 and H19 genes in the regulation of the biologic behavior of this tumor, no research has yet attempt to examine markers across these cluster in relation to melanoma.…”

Section: Discussionmentioning

confidence: 99%

“…This data could be useful to select potential IFN-alpha responders eligible for treatment, while avoiding unnecessary toxicity to non-responders [8,9]. Another treatment, with Vitamin C that plays a crucial role in the suppression of proliferation of several types of cancer, decreases the production of the protein IGF-II.…”

Section: Introductionmentioning

confidence: 97%

Investigation of IGF2/ApaI and H19/RsaI polymorphisms in patients with cutaneous melanoma

Soares

Huber

Rios

et al. 2010

Growth Hormone & IGF Research

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Interferon-α Sensitivity in Melanoma Cells: Detection of Potential Response Marker Genes

Cited by 11 publications

References 19 publications

Interleukins 1α and 1β secreted by some melanoma cell lines strongly reduce expression of MITF‐M and melanocyte differentiation antigens

Interleukins 1α and 1β secreted by some melanoma cell lines strongly reduce expression of MITF‐M and melanocyte differentiation antigens

Detection of Oncofetal H19 RNA in Rheumatoid Arthritis Synovial Tissue

Investigation of IGF2/ApaI and H19/RsaI polymorphisms in patients with cutaneous melanoma

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