Author ORCID Identifier

Date of Graduation


Document Type

Dissertation (PhD)

Program Affiliation


Degree Name

Doctor of Philosophy (PhD)

Advisor/Committee Chair

Andrew Bean

Committee Member

Pramod Dash

Committee Member

Ilya Levental

Committee Member

Andrey Tsvetkov

Committee Member

Jeffrey Frost


The epidermal growth factor receptor (EGFR) variant three (EGFRvIII) mutation is linked with approximately one third of Glioblastoma Multiforme (GBM) tumors and is associated with poor patient prognosis. Persistent signaling due to a lack of the EGFR ectodomain and inefficient degradation have been suggested to underlie the tumorgenic properties of EGFRvIII. I observed that, like the parental EGFR, EGFRvIII is internalized into the intraluminal vesicles of late endosomes / multivesicular bodies (MVBs) but does not follow the canonical pathway by which wild-type EGFR is degraded following MVB fusion with lysosomes. I determined that EGFRvIII is secreted on exosomes, the intraluminal vesicles that are secreted upon MVB fusion with the plasma membrane. This suggested that EGFRvIII is localized in a subset of MVBs that preferentially fuse with the plasma membrane rather than with lysosomes which may account for its decreased degradation.

Astrocytes are a component of the GBM tumor microenvironment with whom tumor cells interact in a paracrine manner. I examined the effect of EGFRvIII-containing exosomes derived from GBM cells on astrocytes and observed that EGFRvIII containing exosomes induce changes in astrocytes that mimic reactive astrogliosis including an increase in glial fibrillary acidic protein (GFAP) and altered astrocyte morphology.

These results reveal novel aspects of the endocytic trafficking of EGFRvIII that underlie its reduced degradation and the mechanism by which it is packaged into exosomes for secretion. Moreover, I show that EGFRvIII secretion on exosomes can facilitate changes in the tumor microenvironment to enable tumor growth.


exosomes, microenvironment, trafficking, endocytosis, late endosome, proliferation, migration, astrocyte



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