Role of reactive astroglia in malignant glioma progression
In this project we are studying how malignant glioma cells induce changes in astrocytes that help tumor growth and invasion. We have focused on two major signaling pathways that are activated in reactive astrocytes (EGFR and NFkB) and have shown that signals from glioma cells regulate those pathways and make astrocytes remodel the neural ECM to facilitate tumor invasion. To further understand this communication between cancer and neural cells, we are using EGFR and NFKB knockout mouse strains, co-culture models, invasion studies in isolated brain tissue and live confocal microscopy to analyze tumor invasion.
In this project we have focused on a unique ECM molecule secreted by malignant gliomas, named fibulin-3. We are studying the signaling mechanisms activated by fibulin-3 that make brain tumors resistant to therapy, including mechanisms of formation of new blood vessels to support tumor growth. This project uses in vitro and in vivo models of angiogenesis, conditional gene expression in the tumor, and live imaging of glioma cells interacting with endothelial and perivascular cells.
Targeting the tumor ECM to disrupt glioma growth and invasion
We have developed novel recombinant proteins and antibodies that can target ECM proteins and block their functions in glioma cells. We are currently developing smaller versions of our targeting reagents, to increase their biodistribution in the brain and anti-tumor efficacy. This translational project follows FDA-proposed guidelines for validation of biological reagents against cancer