Platelet-derived growth factor receptor expression and activation in choroid plexus tumors.

Abstract

Choroid plexus tumors are intraventricular neoplasms predominantly affecting young children. In contrast to choroid plexus papillomas, choroid plexus carcinomas progress frequently, necessitating the development of adjuvant treatment concepts. Platelet derived growth factor (PDGF) signaling has been shown to support growth in a variety of tumors. The finding of PDGF receptor expression in choroid plexus tumors prompted us to elucidate PDGF receptor activation state using a novel method, in situ proximity ligation assay, on formalin-fixed, paraffin-embedded, archival samples of 19 choroid plexus tumors. As assessed by in situ proximity ligation assay, the proportion of phosphorylated PDGF receptor alpha was low in choroid plexus papillomas and choroid plexus carcinomas, whereas phosphorylated PDGF receptor beta was found to be significantly higher in choroid plexus carcinomas. In the immortalized choroid plexus epithelial cell line Z310 expressing PDGF receptor beta, PDGF-BB exhibited a time- and dose-dependent proliferative response, which was significantly attenuated by imatinib (gleevec). In conclusion, our findings suggest that PDGF receptor beta is functionally involved in the biology of choroid plexus tumors and may represent a molecular target for therapy. In addition, this study demonstrates the feasibility and usefulness of in situ proximity ligation assay for monitoring receptor tyrosine kinase activation in formalin-fixed, paraffin-embedded, archival tissues.

• Authors: Björn Koos, Janna Paulsson, Malin Jarvius, Betzabe Chavez Sanchez, Brigitte Wrede, Sonja Mertsch, Astrid Jeibmann, Anne Kruse, Ove Peters, Johannes E A Wolff, Hans-Joachim Galla, Ola Söderberg, Werner Paulus, Arne Ostman, Martin Hasselblatt
• Journal: The American journal of pathology (Am J Pathol) Vol. 175 Issue 4 Pg. 1631-7 (Oct 2009) ISSN: 1525-2191 [Electronic] United States
• PMID: 19717644 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Platelet-Derived Growth Factor
• Receptor, Platelet-Derived Growth Factor alpha
• Receptor, Platelet-Derived Growth Factor beta

Topics

• Animals
• Cell Line
• Cell Line, Transformed
• Cell Proliferation (drug effects)
• Choroid Plexus Neoplasms (metabolism, pathology)
• Epithelial Cells (drug effects, metabolism, pathology)
• Female
• Humans
• Immunohistochemistry
• Infant
• Male
• Papilloma (metabolism, pathology)
• Phosphorylation (drug effects)
• Platelet-Derived Growth Factor (pharmacology)
• Rats
• Receptor, Platelet-Derived Growth Factor alpha (metabolism)
• Receptor, Platelet-Derived Growth Factor beta (metabolism)