1. ¹Abt. Hämatologie, Onkologie und Endokrinologie, Universitäts-Kinderklinik Essen, Germany
2. ²Universitäts-Kinderklinik Marburg, Germany
3. ³Abt. Pädiatrie I, Zentrum für Kinderheilkunde und Jugendmedizin, Klinikum der Georg-August-Universität Göttingen, Germany

Correspondence: L Schweigerer, Abt. Pädiatrie I, Zentrum für Kinderheilkunde und Jugendmedizin, Klinikum der Georg-August-Universität, Robert-Koch-Str. 40, 37075 Göttingen, Germany. E-mail: lothar.schweigerer@med.uni-goettingen.de

⁴These authors contributed equally to this work

Received 16 February 2004; Revised 4 August 2004; Accepted 5 August 2004; Published online 6 December 2004.

Abstract

Amplification of the MYCN oncogene contributes to the malignant progression of human neuroblastomas, but the mechanisms have remained unclear. We have previously demonstrated that N-Myc facilitates angiogenesis by downregulating an angiogenesis inhibitor identified as the inhibin A homodimer activin A. Here, we have sought to define the molecular, biological and clinical consequences of activin A expression in human neuroblastoma. We report that enhanced activin A expression suppresses proliferation and colony formation of human neuroblastoma cells with amplified MYCN in vitro; that it inhibits neuroblastoma growth and angiogenesis in vivo; that it is highly expressed in differentiated, but not undifferentiated human neuroblastomas; and that it correlates with favourable outcome of neuroblastoma patients. Our results indicate that high activin A expression plays an important beneficial role in human neuroblastoma.