Chang M.-C.Chan C.-P.Ho Y.-S.JANG-JAER LEELin P.-S.BOR-RU LINHuang Y.-L.Hahn L.-J.Yeh H.-W.Wang Y.-J.JIIANG-HUEI JENG2021-02-022021-02-0220090904-2512https://www.scopus.com/inward/record.uri?eid=2-s2.0-65649146777&doi=10.1111%2fj.1600-0714.2008.00701.x&partnerID=40&md5=d5da9fdc8e38c5d444629d5c026d550ahttps://scholars.lib.ntu.edu.tw/handle/123456789/545891Background: Tongue cancer metastasis is mainly through blood stream and possibly associated with tumor cell-induced platelet aggregation (TCIPA). Methods: Platelet aggregation was induced by different amounts of SAS tongue cancer cells with/without inhibitors and the latent period for induction of platelet aggregation was recorded. Gene expression was analyzed by reverse transcriptase-polymerase chain reaction. Results: SAS cells (4 × 10 4 to 1 × 10 6 cells/ml) induced platelet aggregation in a cell density-dependent manner. The latent period for induction of platelet aggregation reduced from 11.3 min (2 × 10 5 cells/ml) to 0.9 min (5 × 10 5 cells/ml). The extent of platelet aggregation increased from 39% to 76% by 2 × 10 5 and 5 × 10 5 SAS cells. Pre-treatment of SAS cells with aspirin showed little effect on its induction of platelet aggregation. SAS cells expressed tissue factor (TF) mRNA and the SAS cells-induced TCIPA was inhibited by TF neutralization antibody (5-20 μg/ml), heparin (5-10 U/ml), Hirudin fragment 54-65 (50 μg/ml) and D-Phenylalanyl-L-prolyl-L-arginine chloromethyl ketone. But areca nut (AN, a betel quid component known to generate reactive oxygen species (ROS)) extract showed little effect on TF expression in SAS cells. Pre-treatment with U73122 and 2-aminoethoxydiphenylborate inhibited SAS-induced TCIPA. Interestingly, catalase suppressed SAS cells-induced TCIPA, whereas AN extract enhanced this event. Conclusions: These results suggest that tongue cancer cells may induce TCIPA and enhance tumor metastasis. SAS-induced TCIPA is related to TF secretion, thrombin generation and associated with Phospholipase C-Inositol triphosphate signaling and ROS production. Betel quid chewing may potentially promote tongue cancer metastasis. ? 2008 Blackwell Munksgaard.[SDGs]SDG31 [[6 (3 methoxyestra 1,3,5(10) trien 17beta yl)amino]hexyl] 1h pyrrole 2,5 dione; 2 aminoethoxydiphenylborane; acetylsalicylic acid; catalase; dextro phenylalanylprolylarginyl chloromethyl ketone; heparin; hirudin; inositol trisphosphate; messenger RNA; neutralizing antibody; phospholipase C; thrombin; thromboplastin; article; betel nut; cancer cell; cell density; cell stimulation; gene expression profiling; gene expression regulation; mastication; metastasis potential; priority journal; protein expression; reverse transcription polymerase chain reaction; signal transduction; thrombocyte aggregation; tongue cancer; Areca; Coculture Techniques; Epithelial Cells; Gene Expression Profiling; Gingiva; Humans; Mouth Mucosa; Neoplasm Metastasis; Neoplasm Proteins; Plant Extracts; Platelet Aggregation; RNA, Messenger; Second Messenger Systems; Signal Transduction; Statistics, Nonparametric; Thromboplastin; Time Factors; Tongue Neoplasms; Tumor Cells, Culturedjournal article10.1111/j.1600-0714.2008.00701.x188116712-s2.0-65649146777