Wednesday, July 1, 2020
2-3pm

If you have already pre-registered for NSB seminars, we will use the same Zoom URL. If you haven’t registered yet, please do so here:

https://umass-amherst.zoom.us/webinar/register/WN_-tNREwC5SiKG-s60Lz8uvQ

Once registered, you will receive a link for the Zoom URL. Please bookmark it as it will be used for all future remote NSB seminars.

Chase Cornelison
Assistant Professor, UMass Amherst
Cornelison Group
Biomedical Engineering

“Pathological fluid flow on glial cells in glioblastoma progression and therapy“

Glioblastoma is the most aggressive and deadly form of primary brain cancer. These tumors are characterized by diffuse invasion into the adjacent brain, known as the tumor microenvironment (TME), where tumor cells are more difficult to remove and target with therapy. At the tumor-parenchyma interface, we and others have shown that heightened interstitial fluid flow – the process of fluid transport within tissue – directly stimulates tumor cell invasion. Interstitial flow is known in other cancers to bias TME cells toward pro-tumor phenotypes. We therefore hypothesized that heightened fluid forces stimulate astrocytes and microglia in the brain TME to enhance tumor cell invasion, and this mechanism may provide novel targets for anti-cancer therapy. This seminar will detail our recent work studying effects and implications of pathological fluid forces on glial cells in the brain TME and beyond. We use a collection of in vitro and in vivo tools to study how fluid flow impact glial cells, identify a protein specifically upregulated on glial cells under heightened fluid forces. In a patient-informed model of the invasive brain TME, we find that flow-stimulation of glial cells triggers tumor cell chemotaxis, and this effect is mediated through a flow-dependent, inter-glial signaling mechanism. Blocking this protein is sufficient to limit tumor cell invasion, revealing a novel strategy to prevent tumor spread by targeting of cells in the TME. Furthermore, glial flow-stimulation occurs in the absence of a tumor, which motivates a need to study interstitial flow and its possible role in other neuropathologies. I will end with a brief discussion of glial activation in glioblastoma and our plans to study and leverage these mechanisms for tissue regeneration.