Abstract 2386: High-throughput assessment of the VEGFR2 kinase activity profile in pediatric brain tumor tissue

Abstract

Abstract For enhanced tumor cell survival and progression, tumors depend on angiogenesis. Vascular endothelial growth factor receptor (VEGFR) signaling plays a major part in this process. Previously we generated a comprehensive description of the biological tyrosine kinase activity present in pediatric brain tumor tissue lysates by the application of a peptide microarray containing 144 different tyrosine kinase peptide substrates (Sikkema et al., Cancer Res 2009). The results suggested the presence of activated VEGF receptors in pediatric pilocytic astrocytoma tissue. We hypothesized that this detected VEGFR activity reflects the angiogenic status of the tumor endothelium. In this study we demonstrated that VEGFR2 expression is not present in a pilocytic astrocytoma cell line. Moreover, proximity ligation assays on tumor cryosections showed VEGFR2 phosphorylation, primarily localized on endothelial cells. qRT-PCR analysis of endothelial markers and VEGFRs showed a 10 to 30-fold enrichment of VEGFR2 expression on laser microdissected endothelium compared to whole tumor. Hence, we conclude that the endothelial cells are the high producers of VEGFR2 kinase activity in these tumors and therefore responsible for the VEGFR2 kinase activity that we observed in our kinase activity screens. In conclusion, potential VEGFR kinase substrates present on the peptide microarray are adequately sensitive to pick up enzymatic activity which is present in only a subset of the total cell population within solid tumors such as pilocytic astrocytoma. In the near future, high throughput measurement of enzymatic activity of key players in angiogenesis could make a rapid assessment of the angiogenic profile of a tumor possible. This could serve as an indicator of anti-angiogenic treatment response and result in more personalized anti-angiogenic cancer treatment strategies. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2386.