Low molecular weight heparin downregulates tissue factor expression and activity by modulating growth factor receptor-mediated induction of nuclear factor κB

Fountain, Donna Louise

Biological sciences
February 2013

Thesis or dissertation

© 2013 Donna Louise Fountain. All rights reserved. No part of this publication may be reproduced without the written permission of the copyright holder.

The association between thrombosis and cancer has long been established. Tissue factor (TF), the initiator of the extrinsic pathway in the blood coagulation cascade, has been implicated as one of the most important physiological factors causing such complications. The expression of TF has been observed in many different types of cancer and its increased expression has been shown to correlate with increased incidence of thrombotic events in cancer patients. The use of traditional anticoagulants, such as warfarin, alongside cancer treatments has proved problematic, causing excess bleeding, and has not significantly reduced the risk of thrombosis. Over recent years treatment of cancer patients with low molecular weight heparin (LMWH) has been reported to have beneficial effects that not only reduce the risk of thrombosis but also increase the patient’s life expectancy. This study aimed to examine the influence of a range of LMWH concentrations (0-2000μg/ml) on TF expression, activity, and cell invasiveness in five different cancer cells lines known to express high levels of TF. A decrease in TF mRNA, cellular TF antigen and TF activity was found to correlate with increasing concentrations of LMWH. Additionally LMWH was observed to downregulate nuclear factor κB (NFκB) activity in all cell lines. Further to this, TF expression was suppressed in the presence of LMWH when cells were supplemented with EGF, bFGF and VEGF. Finally, a decrease in cellular invasion was observed following treatment with increasing concentrations of LMWH. These results indicate that LMWH is capable of suppressing TF expression by downregulating NFκB activity through interference with mechanisms involving the action of growth factors. Furthermore, the results indicate that LMWH reduces the rate of cancer cell invasion through a mechanism which appears to be dependent on expression of TF.

Department of Biological Sciences, The University of Hull
Ettelaie, Camille
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