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Tumor-promoting role of signal transducer and activator of transcription (Stat)1 in late-stage melanoma growth

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Abstract

A large-scale gene expression study of melanoma metastases was performed to identify genes involved in late-stage tumor progression. Overall 248 genes, out of more than 47,000 tested, are differentially expressed when comparing peripheral areas (invasion front) with central tumor areas of melanoma metastases. As determined by gene ontology analysis, members of the STAT signaling pathway show significant enrichment. In particular, Stat1 is highly expressed in peripheral compared with central tumor areas. In line with this, stable knockdown of STAT1 in metastatic melanoma cells significantly impairs their migratory and invasive capacity in wounding and matrigel assays. Moreover, STAT1 knockdown affects the metastatic behavior of melanoma cells in a mouse model of melanoma metastasis. Taken together, these data suggest that Stat1 might play a role in late-stage melanoma progression. Interference with the Stat1 pathway could have therapeutic implications for late-stage melanoma patients.

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Acknowledgment

We thank R. Waterstradt and N. Harmel for excellent technical assistance. This study was supported in part by the Erich and Gertrud Roggenbuck Stiftung, Hamburg, Germany.

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Authors and Affiliations

  1. Institute of Medical Biochemistry and Molecular Biology, University of Rostock, 18057, Rostock, Germany

    Julia Schultz

  2. Institute of Immunology and Proteome Center, University of Rostock, 18057, Rostock, Germany

    Dirk Koczan

  3. Systems Biology and Bioinformatics Group, Department of Computer Science, University of Rostock, 18051, Rostock, Germany

    Ulf Schmitz

  4. Department of Dermatology, Allergology and Venereology, University of Lübeck, 23562, Lübeck, Germany

    Saleh M. Ibrahim

  5. Comprehensive Center for Inflammation Medicine, University of Lübeck, Building No. 10, Ratzeburger Allee 160, 23562, Lübeck, Germany

    Dominik Pilch & Manfred Kunz

  6. Department of Dermatology and Allergology, University of Bonn, 53127, Bonn, Germany

    Jenny Landsberg

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  1. Julia Schultz
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  2. Dirk Koczan
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  3. Ulf Schmitz
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  4. Saleh M. Ibrahim
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  7. Manfred Kunz
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Corresponding author

Correspondence to Manfred Kunz.

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10585_2010_9310_MOESM3_ESM.tif

Supplementary Fig. 1: Differential expression of Stat1 and Stat3 in melanoma metastases. Stat1 and Stat3 protein expression was analysed in 10 melanoma metastases by immunohistochemistry. Immunohistochemical staining of three different metastases (Meta1-3) is shown. Magnification x100. (TIFF 28835 kb)

10585_2010_9310_MOESM4_ESM.tif

Supplementary Fig. 2: Differential expression of STAT1 in knockdown and control cells in vivo. Real-time RT-PCR analysis of STAT1 expression in lung and gastrointestinal melanoma metastases of athymic nude mice intravenously injected with control (siCo) and STAT1 knockdown (siSTAT1) melanoma cells. (TIFF 1530 kb)

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Schultz, J., Koczan, D., Schmitz, U. et al. Tumor-promoting role of signal transducer and activator of transcription (Stat)1 in late-stage melanoma growth. Clin Exp Metastasis 27, 133–140 (2010). https://doi.org/10.1007/s10585-010-9310-7

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  • DOI: https://doi.org/10.1007/s10585-010-9310-7

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