Novel report of expression and function of CD97 in malignant gliomas: correlation with Wilms tumor 1 expression and glioma cell invasiveness

Laboratory investigation

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  • 1 Departments of Anatomy and Neurobiology,
  • 4 Pathology, and
  • 2 Neurosurgery/Harold F. Young Neurosurgical Center, Virginia Commonwealth University, Medical College of Virginia Campus, Richmond; and
  • 3 Office of Research, Old Dominion University, Norfolk, Virginia
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Object

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.

Abbreviations used in this paper:ATP = adenosine triphosphate; EGF = epidermal growth factor; GBM = glioblastoma; PDGF = platelet-derived growth factor; qRT-PCR = quantitative reverse transcriptase polymerase chain reaction; SDS = sodium dodecyl sulfate; siRNA = short interfering RNA; VCU = Virginia Commonwealth University; WT1 = Wilms tumor 1.

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Contributor Notes

Current affiliation for Dr. Van Meter: Pediatric Hematology-Oncology, Department of Pediatrics, VCU School of Medicine.

Address correspondence to: William C. Broaddus, M.D., Ph.D., Department of Neurosurgery, Virginia Commonwealth University, P.O. Box 980631, Richmond, Virginia 23298-0631. email: wbroaddus@mcvh-vcu.edu.

Please include this information when citing this paper: published online February 7, 2012; DOI: 10.3171/2011.11.JNS111455.

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