Study On Complex Effecting Mechanism Of Platelet To Tumor Cell Metastasis

The metastasis of tumor cells is an important link in the development of malignant tumors,and it is also one of the main factors of high mortality of tumor patients.In the hematogenous metastasis of tumor cells,tumor cells are facing the surveillance and killing of the immune system,in which natural killer cells(NK cells),as the main initial immune cells,can effectively kill tumor cells in the blood microenvironment and activate subsequent immunity.Whether tumor cells can survive and grow without immune system depends on the coordination of external and internal factors.In the process of hematogenous metastasis,tumor cells contact with platelets and fibrinogen,which promote platelets and fibrinogen to adhere and be coated on their surfaces,and block the recognition and killing of NK cells.However,the timeliness and specific mechanism of its protection mechanism need further study.In the process of tumor cell metastasis,whether the interaction with activated platelets can cause the phosphorylation of STAT6,a signal molecule in tumor cells,and whether this signal molecule affects the survival of tumor cells have not been determined.First of all,the renewal of the "protective layer" of platelets and fibrinogen on the surface of tumor cells in the process of hematogenous metastasis was studied by using fluorescent labeling technique.The results showed that in the process of hematogenous metastasis of tumor cells,the platelet and fibrinogen after the injection of foreign fluorescence markers had the phenomenon of aggregation and detachment on the surface of tumor cells,and there was the phenomenon of re aggregation and detachment after the injection again,suggesting that the "protective layer" of platelet fibrin had the phenomenon of renewal.The experimental results of adding hirudin and plasminogen activator inhibitor-1 suggest that thrombin may be the key enzyme of coagulation and plasmin may be the key enzyme of abscission.Therefore,it can be inferred that the dynamic balance of coagulation(coagulation)and abscission(thrombolysis)exists in the protective layer of platelet fibrin on the surface of tumor cells under the action of two enzymes.In view of the above protective layer,this study blocked the adhesion and renewal by using the polysaccharide of phytoplankton 6803(PCC polysaccharide).In vitro experiments showed that the specific blocking antibodies of PCC polysaccharide,RGD,heparin and integrin P3 could block the protection and renewal of cell surface,and the blocking effect of PCC polysaccharide was more prominent,which was better than that of integrin ?3.Secondly,Western blot was used to investigate the effect of activated platelets on STAT6,a signal molecule in tumor cells.The results showed that the phosphorylation of STAT6 signal molecules in tumor cells was induced by the co incubation of platelets and tumor cells,but not by the deletion of Gas-6 gene.Moreover,the phosphorylation of tumor cells was also weakened after the mer signal receptor molecules were silenced.These results revealed that the platelet derived Gas6 and the mer receptor on the surface of tumor cells may mediate the phosphorylation of STAT6 signal Phosphorylation.SRC and other signal pathways in tumor cells will also be activated at the same time,and the cooperation of each pathway promotes the high expression of signal molecules and contributes to the proliferation and migration of tumor cells.In the effect of different blockers on STAT6 signal,the blocking of SRC pathway can inhibit the phosphorylation of signal molecules,which indicates that SRC may be upstream of STAT6 phosphorylation signal.In this paper,we studied the complex effects on tumor cells from multiple perspectives,from the surface adhesion and protection mechanism to the internal signal molecules,and further understood the contribution of tumor cells to self-protection,proliferation and migration in the process of metastasis.The results showed that the phosphorylation signal of STAT6 was mediated by the Gas6 of platelet and the mer receptor of tumor cells,and the SRC in cell was the upstream signal.Blocking the signal agent had a significant inhibitory effect on the proliferation and migration of cancer cells promoted by platelet.In the future,it can provide help for better study of blood metastasis of tumor cells and provide strong evidence for clinical treatment of cancer.