Article Text
Abstract
Background and aims The PI3K pathway is frequently activated during tumourigenesis through deletion of the tumour suppressor PTEN. In contrast, increased PTEN expression in adipose tissue results in an increase in UCP1 expression and provides metabolic protection from tumourigenesis. This intrinsic protection normally arises from interscapular brown adipose tissue (iBAT) but may also arise from ‘beiging’ of inguinal white adipose tissue (iWAT). The aim of this study was to see if an association existed between UCP1 expression in adipose tissue and paediatric brain tumour growth through elevated PTEN levels.
Methods Two types of medulloblastoma (WNT and group 4) and ependymoma tumour cells were orthotopically xenografted into mice. iBAT and iWAT samples were extracted from tumour and non-tumour bearing mice to examine UCP1 and PTEN expression through QRT-PCR and Western blotting. Haematoxylin and eosin staining and UCP1 antibody immunohistochemistry (IHC) was also used to determine BAT activity in adipose tissue. Thermogenic activity of the adipose tissue was indirectly measured by thermal imaging of mice.
Results iWAT from ependymoma tumour-bearing mice had evidence of beiging and increased UCP1 expression through histology and IHC, while UCP1 expression in iBAT remained high in all mice. An increase in UCP1 gene expression and thermogenesis was observed with spinal metastasis. PTEN expression did not relate to UCP1 expression.
Conclusion Our data indicated mice implanted with aggressive tumours had increased UCP1 expression in iWAT. In conclusion, this pilot study suggests rapidly growing and metastatic brain tumours stimulate metabolic protection via an increase UCP1 expression in iWAT.