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

• Published in: Oncogene Vol. 23; no. 31; pp. 5330 - 5339
• Main Authors: STOVE, Christophe, VANROBAEYS, Frank, DEVREESE, Bart, VAN BEEUMEN, Jozef, MAREEL, Marc, BRACKE, Marc
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing 08-07-2004; Nature Publishing Group
• Subjects: Activin receptors; Activin Receptors - metabolism; Activins - metabolism; Ageing, cell death; Amino Acid Sequence; Annexin A5 - biosynthesis; Apoptosis; Biological and medical sciences; Blotting, Western; Cell Division; Cell Line, Tumor; Cell lines; Cell physiology; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; Dermatology; Dose-Response Relationship, Drug; Follistatin; Follistatin - biosynthesis; Fundamental and applied biological sciences. Psychology; Genes; Genes, Reporter; Growth factors; Heparin; Humans; Immunoblotting; Kinases; Ligands; Luciferases - metabolism; Mass Spectrometry; Medical sciences; Melanocytes; Melanocytes - metabolism; Melanoma; Melanoma - metabolism; Molecular and cellular biology; Molecular Sequence Data; Nuclear medicine; Phosphorylation; Protein Structure, Tertiary; Proteomics; Radiation therapy; Retroviridae - genetics; Reverse Transcriptase Polymerase Chain Reaction; Secretion; Signal Transduction; Smad protein; Time Factors; Transforming growth factor-b; Tumors of the skin and soft tissue. Premalignant lesions; Belgium; Smad protein; Growth; Malignant melanoma; follistatin; melanoma; Smad; Malignant tumor; Antagonist; Inhibition; Activin; Carcinogenesis; Apoptosis
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/sj.onc.1207699

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-beta 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.