Studies On The Cooperation Of Platelet And Fibrinogen In Protecting Tumor Cells

Cancer is one of the most danger diseases of human, as its metastasis, patients suffers a lot and died frequently. Metastasis is a multi-step and highly regulated cascade, which effected by the survival rate of tumor cells in blood mostly. Tumor cell escape form the attacks of immunological factors in blood continue the metastasis. Natural killer cells are essential for the tumor immunity as their special ability to recognize tumor cells from normal cells. However, recent studies show that some tumor cell can escape from the recognition by the help of platelet or fibrinogen. The mechanisms of platelets and fibrinogen in protecting tumor cells from NK cytotoxicity have been discussed for more than 20 years. However, the exact roles and relationships of them in the process are still not clear.In this study, we demonstrate that tumor cells prefer to adhere to fibrinogen than to platelets, and fibrinogen can enhance the adhesion of tumor cells to platelets.β₃ integrins plays an important role in the adhesion of B16F10 to platelets enhanced by fibrinogen. In the presence of thrombin, fibrinogen forms dense fibrin(ogen) layers around tumor cells. Tumor cells can induce platelets to aggregate and form thrombin. Platelets as well as thrombin can help fibrinogen to protect tumor cells from the lethal contact and NK cytotoxicity. Hirudin, a specific inhibitor of thrombin, can reverse the effect of platelets on fibrinogen in blocking NK cytotoxicity. Our results suggest that fibrinogen help platelets adhere to tumor cells, and platelets in turn promote more fibrinogen to aggregate around tumor cells by forming thrombin. They facilitate each other in protecting tumor cells from NK cytotoxicity.In this study, we also detect the ability of chemical modified heparins in abolishing the indirect adhesion of tumor cell and platelet mediated by fibrinogen. By flow cytometry and flow chamber assay, we found that the heparins could effect the adhesion of fibrinogen toβ₃ integrins on the surface of tumor cells or platelets, and inhibit the indirect adhesion. The inhibiting abilities of different heparin are correlated with their structure.