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Clinical & Experimental Metastasis

, Volume 27, Issue 3, pp 133–140 | Cite as

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

  • Julia Schultz
  • Dirk Koczan
  • Ulf Schmitz
  • Saleh M. Ibrahim
  • Dominik Pilch
  • Jenny Landsberg
  • Manfred Kunz
Research Paper

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.

Keywords

Genomics Carcinogenesis Cell migration Mouse models 

Notes

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.

Supplementary material

10585_2010_9310_MOESM1_ESM.doc (284 kb)
(DOC 284 kb)
10585_2010_9310_MOESM2_ESM.doc (46 kb)
(DOC 46 kb)
10585_2010_9310_MOESM3_ESM.tif (28.2 mb)
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 (1.5 mb)
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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Copyright information

© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  • Julia Schultz
    • 1
  • Dirk Koczan
    • 2
  • Ulf Schmitz
    • 3
  • Saleh M. Ibrahim
    • 4
  • Dominik Pilch
    • 5
  • Jenny Landsberg
    • 6
  • Manfred Kunz
    • 5
  1. 1.Institute of Medical Biochemistry and Molecular BiologyUniversity of RostockRostockGermany
  2. 2.Institute of Immunology and Proteome CenterUniversity of RostockRostockGermany
  3. 3.Systems Biology and Bioinformatics Group, Department of Computer ScienceUniversity of RostockRostockGermany
  4. 4.Department of Dermatology, Allergology and VenereologyUniversity of LübeckLübeckGermany
  5. 5.Comprehensive Center for Inflammation MedicineUniversity of LübeckLübeckGermany
  6. 6.Department of Dermatology and AllergologyUniversity of BonnBonnGermany

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