The role of fibrin as a ligand for ICAM-1 and PMN in melanoma adhesion under different shear conditions.

One of the predominant cause of cancer patient death is the metastatic spread of tumor cells. The leading step in melanoma extravasation is the tumor cell adhesion to the endothelium of the capillaries. However, melanoma cells do not express the appropriate adhesion molecules to bind to an activated endothelium. Previous studies have found neutrophils facilitate melanoma cell adhesion under dynamic flow conditions throught the binding of ICAM-1 on melanoma cells and β2 integrins on PMNs. In addition, soluble fibrin (sFn) is a marker for propagated intravascular coagulation and have a dramatical increase in cancer patients' laboratory coagulation inspections . Soluble fibrin molecule has both receptors for Mac-1 on PMNs and ICAM-1 on tumor cell surface which may affect the tumor cell adherence to endothelial wall surface via PMN. The objective of this study is to investigate the role of soluble fibrin on PMN facilitated tumor cell adherence to endothelial wall and how different effects of hydrodynamic shear stress and shear rate affects the force of adhesion to vessel wall.