Effects of thromboxane A2 inhibition on osteogenic sarcoma cell-induced platelet aggregation.
There is evidence that tumors may stimulate platelet aggregation, causing release of thromboxane A2. Thromboxane A2 may potentiate tumor metastasis by stimulating tumor cell growth and proliferation and by enhancing platelet-tumor cell aggregate formation. Despite potential significance of thromboxane A2 in tumor metastasis, agents which inhibit thromboxane A2 synthesis have not been uniformly effective in reducing tumor metastasis. We, therefore, evaluated the effects of a thromboxane A2 receptor antagonist SQ-29,548 compared to those of a thromboxane A2 synthetase inhibitor OKY-046 on osteogenic sarcoma-induced platelet aggregation and thromboxane A2 release. Osteogenic sarcoma cells added to platelet-rich plasma caused complete and irreversible platelet aggregation as well as thromboxane A2 release. Preincubation of platelet-rich plasma with SQ-29,548 (2 to 20 nM) decreased platelet aggregation induced by tumor cells, but it had no effect on thromboxane A2 release. In contrast, preincubation of platelet-rich plasma with OKY-046 (0.1 to 10 microM) had no effect on platelet aggregation despite a decrease in thromboxane A2 synthesis. These results suggest that thromboxane A2 receptor blockers, rather than synthetase inhibitors, may prevent tumor cell-induced platelet aggregation.
Mehta
P
P
Lawson
D
D
Ward
M B
MB
Lee-Ambrose
L
L
Kimura
A
A
D001792:Blood Platelets / Q000378:metabolism; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002478:Cells, Cultured; D005231:Fatty Acids, Unsaturated; D006801:Humans; D006834:Hydrazines / Q000494:pharmacology; D008689:Methacrylates / Q000494:pharmacology; D012516:Osteosarcoma / Q000097:blood*; D010974:Platelet Aggregation; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis
D019086:Bridged Bicyclo Compounds, Heterocyclic; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines; D008689:Methacrylates; D013928:Thromboxane A2; C045749:SQ 29548; C034364:ozagrel