The University of Massachusetts Amherst
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Seminar: Chase Cornelison, University of Massachusetts, Amherst (BME), "Pathological fluid flow in brain cancer progression and therapy"

Date/Time: 

Tuesday, March 10, 2020 - 11:30am

Location: 

LGRT 201

Details: 

Abstract

Interstitial fluid flow is the process by which fluid is transported through the interstitial space of porous biological tissue to deliver nutrients and remove cell waste products. During tumor formation, this homeostasis is disrupted as the ‘leaky’ vasculature deposits fluid in the tumor, increasing fluid pressure and driving fluid convection into the surrounding tissue. We investigate this phenomenon in glioblastoma, the deadliest brain tumor. The rapid progression of glioblastoma is often attributed to its highly invasive nature, and heightened interstitial fluid flow was known to increase glioblastoma cell invasion in vitro. These observations motivated us to translate our experiments in vivo to determine the effects of interstitial fluid flow on tumor-adjacent brain tissue and identify new strategies to limit cancer spread. This seminar will detail work with in vitro and in vivo techniques for modeling and augmenting interstitial flow in the brain as well as implications of pathological fluid shear/flow in brain cancer progression and therapy. We used a technique called convection enhanced delivery to apply interstitial flow directly into brain tumors, showing it increased tumor cell invasion in vivo likely through anisotropic gradient formation around tumor cells. We also identified a protein specifically upregulated in brain regions of high fluid flow. Using a new model of invasive human glioblastoma, we found this protein on neural cells influences tumor cell invasion through a flow-regulated, multi-cellular mechanism and can be targeted for blocking tumor cell invasion. This work therefore uncovered a novel strategy for limiting brain tumor spread by targeting flow stimulation of tumor-adjacent neural cells. Furthermore, fluid flow was found to regulate neural cell responses independent of a tumor, revealing new implications of altered interstitial fluid flow in neural health and disease.

 
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