Novel report of expression and function of CD97 in malignant gliomas: correlation with Wilms tumor 1 expression and glioma cell invasiveness.
OBJECTIVE
The Wilms tumor 1 (WT1) protein-a developmentally regulated transcription factor-is aberrantly expressed in gliomas and promotes their malignant phenotype. However, little is known about the molecular allies that help it mediate its oncogenic functions in glioma cells.


METHODS
The authors used short interfering RNA (siRNA) to suppress WT1 expression in glioblastoma (GBM) cells and evaluated the effect of this on GBM cell invasiveness. Gene expression analysis was then used to identify the candidate genes that were altered as a result of WT1 silencing. One candidate target, CD97, was then selected for further investigation into its role by suppressing its expression using siRNA silencing, followed by proliferation and invasion assays.


RESULTS
WT1 levels were reliably and reproducibly suppressed by siRNA application. This resulted in a significant decrease in cellular invasiveness. Microarray analyses identified the gene products that were consistently downregulated (27) and upregulated (11) with WT1 silencing. Of these, CD97 expression was consistently suppressed across the 3 different GBM cell lines studied and was found on further investigation to significantly impact GBM cell invasiveness.


CONCLUSIONS
Although CD97 expression in gliomas has not been described previously, we conclude that the possible upregulation of CD97 mediated by WT1 promotes cellular invasiveness-one of the most characteristic and challenging aspects of glial tumor cells. Further studies are needed to clarify the nature of this regulation and its impact, as CD97 could represent a novel target for antiglioma therapies.
Department of Anatomy and Neurobiology, Virginia Commonwealth University, Norfolk, VA, USA.
Archana
A
Chidambaram
Helen L
HL
Fillmore
Timothy E
TE
Van Meter
Catherine I
CI
Dumur
William C
WC
Broaddus
D000483:Alleles; D015703:Antigens, CD / Q000235:genetics*; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015536:Down-Regulation / Q000235:genetics; D005091:Exons / Q000235:genetics; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D056726:Genetic Association Studies; D005910:Glioma / Q000235:genetics* / Q000473:pathology; D006801:Humans; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D043562:Receptors, G-Protein-Coupled; D014410:Tumor Stem Cell Assay; D025721:WT1 Proteins / Q000235:genetics*
C095004:ADGRE5 protein, human; D015703:Antigens, CD; D034741:RNA, Small Interfering; D043562:Receptors, G-Protein-Coupled; D025721:WT1 Proteins