STUDIES ON TUMOR-CELL INDUCED PLATELET-AGGREGATION IN HUMAN LUNG-CANCER CELL-LINES

We investigated the ability of human lung cancer cells of different hi stological subtypes to cause platelet aggregation. Tumor-cell-induced platelet aggregation (TCIPA) was studied in vitro in 13 human lung can cer cell lines [small-cell lung cancer (SCLC), squamous-cell lung canc er, large-cell lung cancer, adenocarcinoma and alveolar-cell lung canc er]. Three tumor cell lines failed to aggregate platelets in platelet- rich plasma, whereas platelet aggregation was induced by 12 cell lines when added to washed platelets and minimal amounts of platelet-poor p lasma (0.5% v/v). The thrombin antagonist hirudin inhibited TCIPA in n on-small-cell lung cancer cell lines (NSCLC). In SCLC, TCIPA was fully abolished only when the ADP scavenger apyrase was added to hirudin. T hus ADP and thrombin generation by these tumor cell lines are responsi ble for platelet aggregation. The ability to activate platelets indepe ndently of coagulation factors VII and X was demonstrated for 8 cell l ines. Electron-microscopically, direct tumor-cell/platelet contact was found to be the initiating mechanism of TCIPA in SCLC, whereas tumor- cell/platelet contacts in NSCLC could only be observed at the peak of the aggregation curve. Lung cancer cells activate platelets in vitro b y generation of thrombin and/or ADP.