Blodkärlens betydelse vid glioblastom - molekylära mekanismer och klinisk relevans
Tidsperiod: 2014-01-01 till 2016-12-31
Projektledare: Anna Dimberg
Budget: 3 000 000 SEK
AIM: To understand molecular mechanisms regulating vascular abnormalization in glioblastoma and to identify vascular targets for cancer therapy. BACKGROUND: Glioblastoma are aggressive brain tumors characterized by microvascular proliferation and pleomorphic dysfunctional vessels. It is not clear how distinct gene expression in glioblastoma vessels contributes to abnormal vascular function and cancer progression. We have characterized the transcriptome of human glioblastoma vessels and identified vascular proteins differentially expressed in the vasculature of glioblastoma. This proposal aims to determine how growth factor signaling affects vascular phenotype in glioma, and to investigate the function of differentially expressed proteins. WORKPLAN: Differentially expressed proteins will be evaluated as prognostic markers by analyzing vascular gene expression in glioma tissue microarrays. Functional analysis will be done to determine the role of candidate proteins in vascular biology, angiogenesis, inflammation and vascular permeability. Finally, we will evaluate the role of growth factor signaling and differential gene expression in vascular abnormalization by analyzing human glioma samples and employing experimental models of glioma. SIGNIFICANCE: A deeper understanding of the molecular regulation and functional consequences of vascular abnormalization may provide new tools for inhibiting tumor growth, improving prognosis for patients with glioblastoma.