Multiple PDZ Domain Protein Inhibits Angiogenic Sprouting In Human Umbilical Arterial Endothelial Cells (HUAEC)

Author(s)

Tyler Brown

School Name

South Carolina Governor's School for Science and Mathematics

Grade Level

12th Grade

Presentation Topic

Cell and Molecular Biology

Presentation Type

Mentored

Mentor

Mentor: Fabian Tetzlaff, Vascular Signaling and Cancer, German Cancer Research Center (DKFZ)

Abstract

Like any human tissue, cancerous tissues in tumors require a constant source of oxygen, which is provided by blood vessels. To allow for tumor growth, angiogenesis, or the development of new blood vessel lumen from pre-existing lumen, must occur. A major component of angiogenesis is cell differentiation, and current scientific understanding suggests that Delta-Notch signaling plays an important role in this process. It also suggests that Multiple PDZ domain protein (MPDZ), a scaffolding protein found in endothelial cells, may influence this pathway. Previous research has found that in Human Umbilical Venous Endothelial Cells (HUVEC cells), knockdown of MPDZ results in lower angiogenic activity due to an increase in Delta-Notch signaling. The aim of this research is to determine whether lower levels of angiogenesis occurs in Human Umbilical Arterial Endothelial Cells (HUAEC cells) as well. It was tested through measuring the expression of several Notch target genes (Hey1, Hey2, NRARP, and EphrinB2) using RT:PCRs and through the production of spheroids of HUAEC cells which were induced to sprout under the presence/absence of VEGF and MPDZ control/knockdown. We found that MPDZ knockdown resulted in lower expression of the genes and lower levels of angiogenic sprouting compared to control groups, confirming that MPDZ inhibits angiogenesis in HUAEC cells.

Start Date

4-11-2015 10:45 AM

End Date

4-11-2015 11:00 AM

COinS
 
Apr 11th, 10:45 AM Apr 11th, 11:00 AM

Multiple PDZ Domain Protein Inhibits Angiogenic Sprouting In Human Umbilical Arterial Endothelial Cells (HUAEC)

Like any human tissue, cancerous tissues in tumors require a constant source of oxygen, which is provided by blood vessels. To allow for tumor growth, angiogenesis, or the development of new blood vessel lumen from pre-existing lumen, must occur. A major component of angiogenesis is cell differentiation, and current scientific understanding suggests that Delta-Notch signaling plays an important role in this process. It also suggests that Multiple PDZ domain protein (MPDZ), a scaffolding protein found in endothelial cells, may influence this pathway. Previous research has found that in Human Umbilical Venous Endothelial Cells (HUVEC cells), knockdown of MPDZ results in lower angiogenic activity due to an increase in Delta-Notch signaling. The aim of this research is to determine whether lower levels of angiogenesis occurs in Human Umbilical Arterial Endothelial Cells (HUAEC cells) as well. It was tested through measuring the expression of several Notch target genes (Hey1, Hey2, NRARP, and EphrinB2) using RT:PCRs and through the production of spheroids of HUAEC cells which were induced to sprout under the presence/absence of VEGF and MPDZ control/knockdown. We found that MPDZ knockdown resulted in lower expression of the genes and lower levels of angiogenic sprouting compared to control groups, confirming that MPDZ inhibits angiogenesis in HUAEC cells.