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Suppression of KCMF1 by constitutive high CD99 expression is involved in the migratory ability of Ewing's sarcoma cells

Oncogene volume 25, pages 2795–2800 (2006)Cite this article

Abstract

High CD99 expression levels and rearrangements of the EWS gene with ETS transcription factor genes characterize the Ewing's sarcoma family of tumors (ESFT). CD99 is a cell surface glycoprotein whose engagement has been implicated in cell proliferation as well as upregulation and transport of several transmembrane proteins in hematopoietic cells. In ESFT, antibody ligation of CD99 induces fast homotypic cell aggregation and cell death although its functional role in these processes remains largely unknown. Here, using an RNAi approach, we studied for the first time the consequences of modulated CD99 expression in six different ESFT cell lines, representing the most frequent variant forms of EWS gene rearrangement. CD99 suppression resulted in growth inhibition and reduced migration of ESFT cells. Among genes whose expression changes in response to CD99 modulation, the potassium-channel modulatory factor KCMF1 was consistently upregulated. In a series of 22 primary ESFT, KCMF1 expression levels inversely correlated with CD99 abundancy. Cells forced to express ectopic KCMF1 showed a similar reduction in migratory ability as CD99 silenced ESFT cells. Our results suggest that in ESFT, high CD99 expression levels contribute to the malignant properties of ESFT by promoting growth and migration of tumor cells and identify KCMF1 as a potential metastasis suppressor gene downregulated by high constitutive CD99 expression in ESFT.

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Acknowledgements

We thank Lenka Baskova for help in RQ-PCR. This study was supported by grants from the Austrian Science Fund FWF (#16067-B04), the Austrian government (GEN-AU-Child, contract 200.071/2-VI/1/2001), and the European Commission (PROTHETS, contract LSHC-CT-2004-503036) as well as by funds from the ‘Forschungskommission der Medizinischen Fakultät der Heinrich-Heine-Universität Düsseldorf' and the ‘Madeleine Schickedanz KinderKrebs-Stiftung’.

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Authors and Affiliations

  1. Children's Cancer Research Institute, Kinderspitalgasse, Vienna, Austria

    M Kreppel, D N T Aryee & H Kovar

  2. Institute of Pathology, Heinrich-Heine-University, Moorenstrasse, Dusseldorf, Germany

    K-l Schaefer & C Poremba

  3. Institute of Pathology, Medical University, Waehringer Guertel, Vienna, Austria

    G Amann

  4. Tyrolean Cancer Research Institute, Innrain, Innsbruck, Austria

    R Kofler

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  1. M Kreppel
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Correspondence to H Kovar.

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Kreppel, M., Aryee, D., Schaefer, Kl. et al. Suppression of KCMF1 by constitutive high CD99 expression is involved in the migratory ability of Ewing's sarcoma cells. Oncogene 25, 2795–2800 (2006). https://doi.org/10.1038/sj.onc.1209300

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