Signaling pathways for induction of platelet aggregation by SAS tongue cancer cells--a mechanism of hematogenous metastasis.
BACKGROUND
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 x 10(4) to 1 x 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 x 10(5) cells/ml) to 0.9 min (5 x 10(5) cells/ml). The extent of platelet aggregation increased from 39% to 76% by 2 x 10(5) and 5 x 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 microg/ml), heparin (5-10 U/ml), Hirudin fragment 54-65 (50 microg/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.
Chang
Mei-Chi
MC
Biomedical Science Team, Chang Gung Institute of Technology, Taoyuan, Taiwan.
Chan
Chiu-Po
CP
Ho
Yuan-Soon
YS
Lee
Jang-Jaer
JJ
Lin
Po-Shuen
PS
Lin
Bor-Ru
BR
Huang
Ya-Ling
YL
Hahn
Liang-Jiunn
LJ
Yeh
Hung-Wei
HW
Wang
Ying-Jan
YJ
Jeng
Jiiang-Huei
JH
D001114:Areca; D018920:Coculture Techniques; D004847:Epithelial Cells / Q000378:metabolism; D020869:Gene Expression Profiling; D005881:Gingiva / Q000166:cytology / Q000378:metabolism; D006801:Humans; D009061:Mouth Mucosa / Q000166:cytology / Q000378:metabolism; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000378:metabolism / Q000494:pharmacology; D010936:Plant Extracts / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D015290:Second Messenger Systems / Q000187:drug effects / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D018709:Statistics, Nonparametric; D013925:Thromboplastin / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D014062:Tongue Neoplasms / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D009363:Neoplasm Proteins; D010936:Plant Extracts; D012333:RNA, Messenger; D013925:Thromboplastin