The activation of platelet aggregation by human cholangiocarcinoma cells is mediated through thrombin receptor.
Tumor cell induced platelet aggregation (TCIPA) played an importance role in early state of thrombosis in cancer patients. In addition, TCIPA was recognized as one important step in metastatic cascade. Cholangiocarcinoma, one of the most common cancers in the north-eastern part of Thailand, associated with thrombosis was reported. The authors investigated the effects of cholangiocarcinoma cells on platelet function as measured by platelet aggregation. Primary human cholangiocarcinoma (HuCCA) cells were established in our laboratory. Cells were cultured as standard techniques and grown to confluence until used, after which cells were replaced with fresh medium (Dulbeco Modified Eargle's Medium, DMEM) without serum for 24, 48 and 72 h. Then, the conditioned medium (CM) was collected. CM (24, 48 and 72 h) from HuCCA failed to induce platelet aggregation, whereas, HuCCA pellets induced platelet aggregation and potentiated platelet aggregation induced by submaximal concentration of thrombin. Interestingly, platelet aggregation induced by HuCCA was inhibited by hirudin (thrombin receptor antagonist; 10, 20 and 40 U) in a dose dependent manner. Thus, cholangiocarcinoma cells can induce platelet aggregation in a direct tumor cell-platelet contact via thrombin receptor. Therefore, the use of antiplatelet agents especially via thrombin receptors may help to prevent TCIPA or metastasis by CCA.
Akarasereenont
P
P
Department of Pharmacology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand.
Chotewuttakorn
S
S
Aiamsa-Ard
T
T
Thaworn
A
A
D000328:Adult; D001650:Bile Duct Neoplasms / Q000503:physiopathology*; D001653:Bile Ducts, Intrahepatic; D018281:Cholangiocarcinoma / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000502:physiology*; D018179:Receptors, Thrombin / Q000502:physiology*; D014407:Tumor Cells, Cultured
D018179:Receptors, Thrombin