Tumour cell migration in adamantinomatous craniopharyngiomas is promoted by activated Wnt-signalling.
Activating beta-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 beta-catenin accumulations, suggesting an influence of beta-catenin-dependent signal transduction on the tumour migratory capacity. This hypothesis was tested by suppressing beta-catenin expression in six primary human adaCP cell cultures using small interfering RNA (siRNA) directed against the beta-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 beta-catenin TCF signalling in colorectal cancer cells and a key component of filopodia, is also involved in this process. beta-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.
Department of Neuropathology, University Hospital of Erlangen, Schwabachanlage 6, Erlangen, Germany.
Annett
A
Hölsken
Michael
M
Buchfelder
Rudolf
R
Fahlbusch
Ingmar
I
Blümcke
Rolf
R
Buslei
D015153:Blotting, Western; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002465:Cell Movement / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D003397:Craniopharyngioma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism; D010911:Pituitary Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D034741:RNA, Small Interfering; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D051153:Wnt Proteins / Q000235:genetics* / Q000378:metabolism; D014945:Wound Healing / Q000235:genetics; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
D002352:Carrier Proteins; D008840:Microfilament Proteins; D034741:RNA, Small Interfering; D051153:Wnt Proteins; D051176:beta Catenin; C020324:fascin