CROSSTALK BETWEEN COAGULATION AND RECEPTOR MEDIATED TUMOR CELL ADHESION TO ENDOTHELIUM UNDER HYDRODYNAMIC SHEAR.

Open Access
Author:
Ozdemir, Tugba
Graduate Program:
Bioengineering
Degree:
Master of Science
Document Type:
Master Thesis
Date of Defense:
None
Committee Members:
  • Cheng Dong, Thesis Advisor
Keywords:
  • melanoma metastasis
  • fibrin
  • coagulation
  • adhesion receptors.
Abstract:
Coagulation is a programmed cascade of events known to be playing a pivotal role in immune surveillance as well as the blood clot formation. Although, coagulation is known to be crucial for immune surveillance, this process is considered to be linked with tumor metastasis in recent studies. Since the primary coagulation initiator thrombin generation needed to be activated by inflammatory cytokines and tissue factors it is not surprising to face increased coagulation parameters in tissue factor expressing tumor microenvironment and innate immune system components such as platelets and PMNs(polymorphoneutrophils). During their travel in hydrodynamic flow, tumor cells need to adhere in order to prevent from anoikis and spread through distant organs. On the other hand, tumor cells do not have appropriate receptors to adhere to the endothelium by themselves. They need to anchor themselves through different mediators such as the components of host immune system which are capable of travelling freely in the body. For this reason PMNs are known to be the best candidates for metastatic tumor cells. PMNs are immune cells which have the capability to adhere to endothelium via specific Selectins and Integrins. They are capable of not only resisting high shear conditions of hemodynamic flow but also transmigrating through the endothelial wall and travel to distant organs in which they are needed. In this study, we are seeking to model the above proposed hydrodynamic tumor microenvironment with creating a steady state hydrodynamic flow in vitro by putting all the possible components together and investigate the adhesion mechanism of highly metastatic tumor cells to endothelium.