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  • Original Paper
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Melanoma cells secrete follistatin, an antagonist of activin-mediated growth inhibition

Oncogene volume 23, pages 5330–5339 (2004)Cite this article

Abstract

Using a proteomic approach to screen for new growth factors released by melanoma cells, we identified follistatin as a major heparin-binding factor in medium conditioned by the Bowes melanoma cell line. Since follistatin is primarily studied in relation to its neutralization of activin, a member of the transforming growth factor-β family of ligands, the expression and function of this receptor system was investigated in a panel of melanoma cell lines and melanocytes. All cell lines expressed activin receptors and showed phosphorylation of Smad signal transduction molecules upon treatment with activin. Secretion of follistatin, either native or after retroviral transduction, efficiently prevented Smad activation or activation of an activin-responsive luciferase reporter construct. In melanocytes, activin treatment led to growth inhibition and induction of apoptosis. These effects were counteracted by cotreatment with follistatin. In summary, we characterized the activin–activin receptor system in melanocytes and melanoma cell lines and found that secretion of follistatin by melanoma cells may represent an effective way to circumvent activin's negative regulatory effects.

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Abbreviations

CM:

conditioned medium

EGFP:

enhanced green fluorescence protein

FS:

follistatin

IRES:

internal ribosomal entry site

LIE:

LZRS-IRES-EGFP

PMA:

phorbol 12-myristate 13-acetate

TGF-β:

transforming growth factor-β

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Acknowledgements

We thank Dr Lambert and Martine De Mil for providing melanocyte cultures, Veronique Stove for help with retroviral transduction, Dr Shimasaki for the follistatin construct, Dr Nolan for the Phoenix amphotropic cell line, Dr Berx for CAGA and pUT reporter constructs and Isabel Vandenberghe for N-terminal sequencing. This work was supported by the Sportvereniging tegen Kanker and by the Belgian Federation for the Study of Cancer (BVSK). Christophe Stove is a research assistant with the Fund for Scientific Research-Flanders, which also provided the mass spectrometric instrumentation (Grant G.0312.02).

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  1. Christophe Stove

    Present address: Department for Molecular Biomedical Research, VIB-Ghent University, FSVM Building, Technologiepark 927, 9052, Zwijnaarde, Belgium

Authors and Affiliations

  1. Department of Radiotherapy and Nuclear Medicine, Laboratory of Experimental Cancerology, Ghent University Hospital, De Pintelaan 185, Ghent, 9000, Belgium

    Christophe Stove, Marc Mareel & Marc Bracke

  2. Laboratory of Protein Biochemistry and Protein Engineering, Ghent University, KL Ledeganckstraat 35, Ghent, 9000, Belgium

    Frank Vanrobaeys, Bart Devreese & Jozef Van Beeumen

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Correspondence to Marc Bracke.

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Stove, C., Vanrobaeys, F., Devreese, B. et al. Melanoma cells secrete follistatin, an antagonist of activin-mediated growth inhibition. Oncogene 23, 5330–5339 (2004). https://doi.org/10.1038/sj.onc.1207699

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