Using the Chick Embryo Brain as a Model for In Vivo and Ex Vivo Analyses of Human Glioblastoma Cell Behavior

The scope of our research is to try to uncover mechanisms that promote glioblastoma cell spread in brain tissue. Specific questions revolve around differences in glioblastoma cell types or states and molecular mechanisms that promote these cells to be highly invasive. For example, how does L1CAM expression promote invasiveness?

Both in vitro and in vivo models are insufficient for accurately analyzing glioblastoma cell behavior. In vitro models almost certainly modify and oversimplify in vivo cell behaviors. While in vivo models do not allow for easy observation of behaviors as they occur, instead allowing for analyses after the behaviors have occurred.

We have shown that the chick embryo brain is a good model for studying human brain cancer cell behavior both in vivo and in ex-vivo slice cultures. We also have established that L1CAM expression by glioblastoma cells can have profound effects on cell proliferation, invasion, and arrangement within the tumor. Besides several advantages of using chick embryos, our ex-vivo spheroid protocol introduces cells onto live slices with no additional damage, whereas other methods of cell introduction involve piercing the tissue and implanting cells.

Additionally, the protocol allows for live time-lapse imaging that in vivo techniques do not. Our findings suggests that the chick embryo is a good model for cancer research, particularly brain cancer, and is extremely beneficial for the scientific community, as it is much more readily available to those who may not have the funds, facilities, or expertise for rodent models. We will continue to focus on molecular mechanisms that control glioblastoma cell invasiveness in brain tissue, particularly along blood vessels.

Another crucial question is whether glioblastoma stem cells are a distinct and stable phenotype or a functional state that can be adopted when needed. That has huge implications for treatments.