Thread by @HerveyJumper

Patients with #glioma often experience altered cognition but it was unknown whether tumors remodel or destroy neuronal circuits in the human brain. New, open access #CancerNeuroscience paper: nature.com/articles/s4158….

In our study led by talented @NeurosurgUCSF post doc @SarithaKrishnaa and collaborators @michelle_monje, @DavidJBrang @LabRaleigh @AnnetteMolinar2, we found that glioblastomas remodel circuits.

Intraoperative recordings in awake people with left hemisphere #GBM show us that speech production activates glioma-infiltrated cortex, and GBM remodels speech circuitry so that producing speech activates all of the glioma-infiltrated cortex.

Some parts of the tumor are more functionally connected to the brain than others. These areas of high functional connectivity contain tumor cells that are particularly responsive to neuronal activity-regulated growth signals.

And this subpopulation of glioblastoma cells found in areas of high functional connectivity express the synaptogenic factor thrombospondin (TSP-1), which promotes synapse formation and neural circuit remodeling.

The synaptogenic population of glioblastoma cells proliferate, invade, and establish tumor microtubes in response to neurons in vitro and in vivo.

Glioblastoma connectivity in patients is strongly associated with shortened survival, highlighting the importance of neuron-glioma interactions.

Targeting TSP-1 represents a promising new therapeutic strategy to disrupt neuron-glioma interactions.
nature.com/articles/d4158…