Date of Graduation

5-2022

Document Type

Thesis

Degree Name

Bachelor of Science in Biomedical Engineering

Degree Level

Undergraduate

Department

Biomedical Engineering

Advisor/Mentor

Muldoon, Timothy J.

Abstract

Colorectal cancer is the third most common cancer in the world, and it is the fourth most common cause of cancer related death (1). There have been many significant advancements regarding the treatment of cancer which aim to shrink the size of tumors in patients. However, there is still more that needs to be understood about the many different factors that play a role in colorectal cancer development.

Angiogenesis is the process of forming new blood vessels from existing ones and it requires breaking down and remodeling of the extracellular matrix (ECM) in order to allow endothelial cells to migrate and invade into the surrounding tissue so that new blood vessels can successfully sprout. Among the many signals that initiate and nurture angiogenesis, vascular endothelial growth factor (VEGF) is the one of interest.

Matrix metalloproteinases (MMPs) are endopeptidases that break peptide bonds of non-terminal amino acids. Among all the classes of MMPs, it has been found that membrane-type MMPs, such as MMP14, play a role in the process of angiogenesis. MMPs are known to enhance angiogenesis by releasing ECM bound angiogenic growth factors such as VEGF (4).

The most widely used chemical carcinogen used to induce colon tumors in mice is azoxymethane (AOM). 5-fluorouracil (5-FU) is one of the anti-cancer drugs used to treat colorectal cancer (6). The AOM mouse model will be used to study the effects of colorectal cancer and the effects of 5-FU treatment.

The goal of this research was to understand how 5-FU treatment of AOM mice affect the gene expression of VEGF and HIF-1 and the quantification of MMP14, a membrane-type MMP, in colon tumors. Since it is known that VEGF and HIF-1 play a significant role in angiogenesis, it is important to investigate the role that MMPs play in angiogenesis as well.

Keywords

angiogenesis; MMP14; VEGF; HIF-1; Nestin; colorectal cancer

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