Tenascin-C expression contributes to pediatric brainstem glioma tumor phenotype and represents a novel biomarker of disease.

ABSTRACT: Diffuse intrinsic pontine glioma (DIPG), an infiltrative, high grade glioma (HGG) affecting young children, has the highest mortality rate of all pediatric cancers. Despite treatment, average survival is less than twelve months, and five-year survival under 5%. We previously detected increased expression of Tenascin-C (TNC) protein in DIPG cerebrospinal fluid and tumor tissue relative to normal specimens. TNC is an extracellular matrix (ECM) glycoprotein that mediates cell-matrix interactions, guides migrating neurons during normal brain development and is thought to maintain the periventricular stem cell niche in the developing brain. Tumor TNC expression is reported in adult glioma and other cancers. However, the pattern and effects of TNC expression in DIPG has not been previously explored. Here, we characterize TNC expression in patient derived pediatric supratentorial HGG (n?=?3) and DIPG (n?=?6) cell lines, as well as pediatric glioma tumor (n?=?50) and normal brain tissue specimens (n?=?3). We found tumor specific TNC gene and protein overexpression that directly correlated with higher tumor grade (WHO III and IV, p?=?0.05), H3K27?M mutation (p?=?0.012), shorter progression free survival (p?=?0.034), and poorer overall survival (0.041) in association with these factors. TNC knockdown via lentiviral shRNA transfection of HGG (n?=?1) and DIPG (n?=?3) cell lines resulted in decreased cell proliferation, migration, and invasion in vitro (p?

SUBMITTER: Qi J 

PROVIDER: S-EPMC6518697 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature