Expression Of The Thrombin And Protease-activated Receptor(PAR)-1 In Patients With Malignant Pleural Effusion

Background Tumor cells growth and metastasis can be induced via elicitation of protease-activated receptors(PAR) with serine proteases such as thrombin.Objective To detect and compare the expression levels of thrombin in serum and pleural effusion, and to investigate whether tumor cells in malignant pleural effusion expresses protease-activated receptor-1, then to explore the tumor biological effects of thrombin and PAR-1 in patients with malignant pleural effusion.Methods The serum and pleural effusion thrombin-antithrombin complexes(TAT) levels were determined in 10 patients and controls by ELISA;Reverse transcriptase-polymerase chain reaction(RT-PCR) wereperformed to detect PAR-1 expression using the cultured tumor cells from malignant pleural effusions of 10 patients.Results Serum levels of TAT was significantly higher in patients with malignant pleural effusion than in healthy controls(P<0.005).Serum levels of TAT was also significantly higher than pleural fluid in patients with MPE(P<0.01), there was no significant correlation between the serum and pleural fluid TAT levels in patients with malignant pleural effusion(r=-0.083, P>0.05). Pleural fluid levels of TAT was significantly higher in patients with malignant pleural effusion than in tuberculous pleurisy controls(P<0.05). PAR-1 was expressed in 6 of the 8 adenocarcinoma cells in contrast to 0 of the 2 squamous cells.Conclusion Serum and pleural fluid TAT levels both elevated significantly in patients with malignant pleural effusion, showing that thrombin can be activated in circulating blood, also can be activated in pleural effusion locally by tumor cells and/or tumor-associated host cells. Levels of thrombin seems higher in serum than in pleural fluid, this result was not coincident with Schiller' s report previously, that showed higher levels of F1+2 in malignant effusion than in serum. It might because that TAT levels in pleural fluid affected by antithrombinâ…¢ and other factors. In the present study, we confirmed first time that tumor cells in malignant pleural effusion can express PAR-1. Adenocarcinoma cells showed overexpression especially, meanwhile adenocarcinoma cell lung canceroften shows hematogenous and pleural metastatic potential early. Activation of thrombin and expression of PAR-1 was suggested to contribute in tumor cells growth and metastatic dissemination.