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Tumour cell migration in adamantinomatous craniopharyngiomas is promoted by activated Wnt-signalling

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Abstract

Activating β-catenin mutations with aberrant cytoplasmic and nuclear protein accumulation are hallmarks of adamantinomatous craniopharyngiomas (adaCP). These tumours tend to be associated with unfavourable and occasionally disastrous sequelae, as they invade adjacent brain structures such as the hypothalamus. The peculiar digitate growth pattern does not always allow gross surgical removal often leading to recurrence. The tips of invading adaCP epithelium harbour cell clusters with nuclear β-catenin accumulations, suggesting an influence of β-catenin-dependent signal transduction on the tumour migratory capacity. This hypothesis was tested by suppressing β-catenin expression in six primary human adaCP cell cultures using small interfering RNA (siRNA) directed against the β-catenin gene (CTNNB1). Tumour cell migration was significantly reduced in Boyden chamber and wound-healing experiments following siRNA treatment. We further showed that fascin, a target gene of β-catenin TCF signalling in colorectal cancer cells and a key component of filopodia, is also involved in this process. β-Catenin accumulating tumour cells co-express fascin and fascin mRNA levels can be significantly down-regulated in adaCP cultures treated with CTNNB1 siRNA. Furthermore, migration experiments showed a significantly lower cell motility of adaCP tumour cells in vitro when transfected with fascin siRNA. This suggests that activated Wnt-signalling serves as a promoter of the epithelial migration machinery by regulating target molecules such as fascin in adaCP tumour cells.

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Acknowledgments

We thank Verena Schmidt for her excellent technical assistance. Additionally, we are indebted to Nadine Schmiedel, Diana Maron, Silke Sterner and Katharina Porsche for performing immunohistochemical stainings and Jeremy Wiles for proof-reading the manuscript. This work was supported by the ELAN fund (08.09.08.1) of the University Hospital Erlangen (to AH and RB).

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Authors and Affiliations

  1. Department of Neuropathology, University Hospital of Erlangen, Schwabachanlage 6, 91054, Erlangen, Germany

    Annett Hölsken, Ingmar Blümcke & Rolf Buslei

  2. Department of Neurosurgery, University Hospital of Erlangen, Erlangen, Germany

    Michael Buchfelder

  3. International Neuroscience Institute, Hannover, Germany

    Rudolf Fahlbusch

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  1. Annett Hölsken
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  2. Michael Buchfelder
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  3. Rudolf Fahlbusch
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  4. Ingmar Blümcke
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  5. Rolf Buslei
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Correspondence to Rolf Buslei.

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Hölsken, A., Buchfelder, M., Fahlbusch, R. et al. Tumour cell migration in adamantinomatous craniopharyngiomas is promoted by activated Wnt-signalling. Acta Neuropathol 119, 631–639 (2010). https://doi.org/10.1007/s00401-010-0642-9

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  • DOI: https://doi.org/10.1007/s00401-010-0642-9

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