The activation of platelet aggregation by human cholangiocarcinoma cells is mediated through thrombin receptor. 2001

P Akarasereenont, and S Chotewuttakorn, and T Aiamsa-Ard, and A Thaworn
Department of Pharmacology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand.

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.

UI MeSH Term Description Entries
D008297 Male Males
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D010974 Platelet Aggregation The attachment of PLATELETS to one another. This clumping together can be induced by a number of agents (e.g., THROMBIN; COLLAGEN) and is part of the mechanism leading to the formation of a THROMBUS. Aggregation, Platelet
D005260 Female Females
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000328 Adult A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available. Adults
D001650 Bile Duct Neoplasms Tumors or cancer of the BILE DUCTS. Bile Duct Cancer,Cancer of Bile Duct,Cancer of the Bile Duct,Neoplasms, Bile Duct,Bile Duct Cancers,Bile Duct Neoplasm,Cancer, Bile Duct,Cancers, Bile Duct,Neoplasm, Bile Duct
D001653 Bile Ducts, Intrahepatic Passages within the liver for the conveyance of bile. Includes right and left hepatic ducts even though these may join outside the liver to form the common hepatic duct. Bile Duct, Intrahepatic,Duct, Intrahepatic Bile,Ducts, Intrahepatic Bile,Intrahepatic Bile Duct,Intrahepatic Bile Ducts
D014407 Tumor Cells, Cultured Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely. Cultured Tumor Cells,Neoplastic Cells, Cultured,Cultured Neoplastic Cells,Cell, Cultured Neoplastic,Cell, Cultured Tumor,Cells, Cultured Neoplastic,Cells, Cultured Tumor,Cultured Neoplastic Cell,Cultured Tumor Cell,Neoplastic Cell, Cultured,Tumor Cell, Cultured
D018179 Receptors, Thrombin A family of proteinase-activated receptors that are specific for THROMBIN. They are found primarily on PLATELETS and on ENDOTHELIAL CELLS. Activation of thrombin receptors occurs through the proteolytic action of THROMBIN, which cleaves the N-terminal peptide from the receptor to reveal a new N-terminal peptide that is a cryptic ligand for the receptor. The receptors signal through HETEROTRIMERIC GTP-BINDING PROTEINS. Small synthetic peptides that contain the unmasked N-terminal peptide sequence can also activate the receptor in the absence of proteolytic activity. Thrombin Receptors,TRAP Peptide,Thrombin Receptor,Thrombin Receptor Activating Peptide Ligand,Thrombin Receptor Activating Peptides,Thrombin Receptor Activator Peptide,Peptide, TRAP,Receptor, Thrombin

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