BioProject

Glioblastoma multiforme is the most common and aggressive form of brain cancer. More...

Glioblastoma multiforme is the most common and aggressive form of brain cancer. The use of oncolytic HSV-1 (oHSV) to selectively target brain cancer cells leading to their lytic destruction has shown to be very promising in a preclinical setting, but is lacking efficacy in clinical trials. Cyr61, a secreted extracellular matrix protein which functions to promote angiogenesis, migration, proliferation and tumorigenesis, was found to be upregulated rapidly following oHSV infection. Here we show, using microarray analysis, that Cyr61 expression leads to the induction of several genes with type 1 interferon function. We show that Cyr61 mediated type 1 IFN induction is through its interaction with integrin alpha6beta1 on the cell surface and results in oHSV inhibition, reducing the efficacy of this therapy. We used microarray to detail the global program of gene expression underlying Cyr61 mediated oncolytic HSV-1 inhibition and identified distinct classes of up-regulated genes during this process. Overall design: Tetracycline-Inducible glioma cells expressing Cyr61 protein in the presence of doxycycline were treated with or without doxycycline for 24 hours. RNA was extracted and hybridized on Affymetrix microarray. Two groups: ± dox to induce cyr61, performed in triplicate. Less...