Evaluating the Impact of Microenvironmental Elasticity on the Stem Cell Phenotype in Malignant Glioma
Justin D. Lathia, Ph.D. at the Cleveland Clinic
Malignant gliomas provide treatment challenges due to their infiltrative nature and high propensity for recurrence, despite aggressive treatments including surgery, radiation, and chemotherapy. Recent work has suggested gliomas have a hierarchal organization with a self-renewing glioma stem cell (GSC) that is therapeutically resistant. Understanding how the stem cell state is maintained in gliomas is an immediate priority and may be at the core of why these tumors are difficult to treat. The interaction between the GSCs and their microenvironment regulates the stem cell state. Focus has been on the biological factors within these microenvironments but the physical contribution has yet to be investigated. Clinical observations suggest that glioma therapies (surgery and radiation) alter the elasticity of the brain. In this application, Dr. Lathia hypothesizes that the physical forces within the microenvironment can contribute to the stem cell state and that anti-glioma therapies can be developed by uncoupling the ability for a cell to respond to mechanical stiffness (via myosin II). Dr. Lathia’s studies will take advantage of the access to primary tumor tissue and utilize state of the art models which include in vivo live imaging. His team will address how the physical microenvironment impacts the stem cell state and validate a novel anti-glioma therapy based on uncoupling how GSCs respond to elasticity which can be rapidly translated into clinical practice.
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