Date of Award

7-11-2015

Degree Type

Thesis

Degree Name

M.Sc.

Department

Chemistry and Biochemistry

First Advisor

Boffa, Michael

Keywords

Angiogenesis, Cancer, TAFI, Thrombomodulin

Rights

CC BY-NC-ND 4.0

Abstract

Thrombomodulin (TM) is known mostly for its role in the regulation of hemostasis, but it has also been shown to play an antimetastatic role in cancer. A previous study showed that the anitmetastatic effects of TM were dependent on thrombin binding. However, it is not known which substrate of thrombin-TM, protein C or TAFI, is responsible for these antimetastatic effects. We hypothesized that TAFI is responsible for the antimetastatic effects of TM, specifically tumour angiogenesis, due to its role in the inhibition of pericellular plasminogen activation. We determined the effect of TAFIa on tumour angiogenesis through inhibition of TAFIa and manipulation of cofactor ability of TM. We found inhibition of TAFIa resulted in increased proliferation, invasion, tube formation, and ECM proteolysis. We also found an inhibitory effect of TAFI activation by thrombin-TM on tube formation and ECM proteolysis. Our results suggest that TAFIa inhibits tumour angiogenesis in breast cancer cells.

Share

COinS