TWIST-1 Is Overexpressed in Neoplastic Choroid Plexus Epithelial Cells and Promotes Proliferation and Invasion

¹Institute of Neuropathology and ²Integrated Functional Genomics, IZKF, University Hospital Münster, Münster, Germany; ³Department of Pediatric Oncology, University of Regensburg, Regensburg, Germany; ⁴Children's Cancer Hospital, MD Anderson Cancer Center, Houston, Texas; and ⁵School of Health Sciences, Purdue University, West Lafayette, Indiana

^* To whom correspondence should be addressed. E-mail: hasselblatt{at}uni-muenster.de.

	Abstract

The pathogenesis of choroid plexus papillomas, intraventricular papillary neoplasms most often occurring sporadically in children and young adults, remains poorly understood. To identify pathways operative in the development of choroid plexus papillomas, gene expression profiles obtained from laser-microdissected human choroid plexus papilloma cells (n = 7) were compared with that of normal choroid plexus epithelial cells laser microdissected from autopsy tissue (n = 8). On DNA microarray data analysis, 53 probe sets were differentially expressed in choroid plexus papilloma tumor cells (>7-fold). Up-regulation of TWIST1, WIF1, TRPM3, BCLAF1, and AJAP1, as well as down-regulation of IL6ST was confirmed using quantitative reverse transcription-PCR. Knockdown of Twist1 gene expression in the rat choroid plexus epithelial cell line Z310 significantly reduced proliferation as assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and cell invasion in a Matrigel assay, whereas cell migration was not affected. Screening for expressional changes of cancer-related genes upon Twist1 knockdown revealed up-regulation of Cdkn1a, Cflar, and Serpinb2 and down-regulation of Figf. To conclude, using gene expression profiling, several genes differentially expressed in human choroid plexus papillomas could be identified. Among those, TWIST1 is highly expressed in choroid plexus papillomas and promotes proliferation and invasion. [Cancer Res 2009;69(6):2219–23]

Key Words: pediatric neuro-oncology, choroid plexus papilloma, laser-microdissection, pathogenesis, p53 signaling