Electronic Thesis and Dissertation Repository

Degree

Master of Science

Program

Medical Biophysics

Supervisor

Dr. John D. Lewis

Abstract

The growth of a tumor depends on de novo angiogenesis, which involves multiple signaling cascades and is also a target for many anti-angiogenic therapies. Epidermal growth factor like (EGFL7), is a protein that is exclusively expressed by endothelial cells during angiogenesis and is necessary for the proper assembly of a sprout. However, EGFL7 is also upregulated in many tumors such as glioma and non-small cell lung cancer, associated with poor patient prognosis. We have previously shown that EGFL7 expression by tumor cells inhibits tumor angiogenesis, which is contrary to its requirement for angiogenesis when expressed by endothelial cells. As a result, the objective of this research is to understand the basis of this differential regulation. We hypothesize that the differential effects of EGFL7 on angiogenesis is due to the presence of alternative transcripts in HT1080 tumor cells. Here, I demonstrate that endothelial cells express two families of transcripts, TSS1 and TSS2 families, which are transcribed from two different transcriptional start sites. In HT1080 tumor cells however, only TSS2 families of transcripts are produced. Importantly, a novel non-coding transcripts in both TSS1 and TSS2 family is identified. Knocking down TSS2 transcripts in tumor cells resulted in enhanced angiogenesis. Result from this thesis; identify novel differential EGFL7 transcripts expressed in HT1080 tumor cells, which inhibits angiogenesis.


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