Tumor Cell-Induced Platelet Aggregation in Vitro by Human Pancreatic Cancer Cell Lines

Abstract

Background: Tumor cell-induced platelet aggregation (TCIPA) is considered to be a critical step in hematogenous metastasis. Methods: TCIPA was studied in vitro in six human pancreatic carcinoma cell lines (PC 3, PC 44, AsPC1, BxPC3, Capan2, Pane1). Results: Whereas all cell lines induced aggregation of washed platelets in the presence of minimal amounts of platelet-poor plasma, five cell lines also induced aggregation of platelets in platelet-rich plasma. The thrombin-antagonist hirudin inhibited TCIPA in all cell lines, indicating that TCIPA is thrombin-dependent. Since pretreatment of tumor cells with phospholipase A₂ or C inhibited TCIPA, the thrombin-generating activity might be confined to the tumor cell surface. Further support for a prothrombinase activity was provided by the observation that all cell lines were able to induce the aggregation of washed platelets after addition of purified coagulation factors II and V. Conclusions: Pancreatic carcinoma cells are able to induce platelet aggregation via activation of thrombin. This might support metastasis in pancreatic cancer and possibly explain the incidence of thrombosis in this tumor.

Key Words:

• Aggregation
• metastasis
• pancreatic cancer
• platelets
• thrombin