Date of Award

8-2015

Degree Type

Thesis

Degree Name

Master of Science

Department

Biology

Program

Biology

First Advisor/Chairperson

Dr. Robert Belton

Second Advisor

Dr. Robert Winn

Third Advisor

Dr. Erich Ottem

Fourth Advisor

Dr. Richard Rovin

Abstract

Glioblastoma multiforme (GBM) is an aggressive central nervous system malignancy that commonly causes immune suppression in patients to avoid immune recognition and clearance. This complicates treatment options and limits the effectiveness of immunotherapy strategies. Interestingly, GBM formation can stimulate the neurogenic subventricular zone of the cerebral cortex and causes the proliferation and migration of neural stem cells (NSCs) towards the tumor. This migration reflects the NSC wound repair response following CNS injury. Studies using NSCs surgically implanted into GBM tumors showed decreased tumor growth and increased animal survival in mice; however, the mechanisms underlying these anti-tumor properties of NSCs are unknown. Here we performed co-culture proliferation assays in combination with gene expression analysis to show that there is a two-way communication between the NSCs and glioma cells that results in decreased glioma proliferation and changes to survival and apoptotic-related gene expression. These changes correlated with increased expression of tumor necrosis factor (TNF) superfamily death receptor ligands by the NSCs. NSCs also were found to express many immune-related cytokines and chemokines involved in immune signaling, suggesting a potential role in mediating anti-tumor immune responses. These results provide the first mechanistic evidence of NSC-mediated tumor suppression.

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