Inhibitory effects of DN-9693 on platelet-enhanced tumor cell attachment to cultured endothelium.
The effects of DN-9693, a platelet aggregation inhibitor, on tumor cell attachment to endothelium were investigated to clarify its inhibitory action on metastasis. The role of platelets in the attachment of murine metastasizing tumor cells to endothelium was first examined in vitro. Morphological studies and quantitative isotope measurements revealed that tumor-cell-activated platelets significantly enhanced tumor cell attachment to the endothelium. This amplification is considered to depend on morphological and functional changes of endothelial cells: activated platelets may accelerate endothelial retraction, exposing more reactive subendothelium, and may increase the adhesiveness of endothelial cells. The platelet-enhanced tumor cell attachment to the endothelium was inhibited in the presence of DN-9693. The pretreatment of endothelial cells with the compound was also effective in inhibiting cell attachment. These data suggest that the inhibitory effects of DN-9693 on metastasis are in part mediated by the prevention of tumor cell attachment to the vascular endothelium.
Tohgo
A
A
Research Institute, Daiichi Pharmaceutical Co., Ltd., Tokyo, Japan.
Tanaka
N G
NG
Osada
Y
Y
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000818:Animals; D001792:Blood Platelets / Q000648:ultrastructure; D002118:Calcium / Q000494:pharmacology; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects*; D008175:Lung Neoplasms / Q000503:physiopathology; D008297:Male; D008546:Melanoma, Experimental / Q000556:secondary; D051379:Mice; D008810:Mice, Inbred C57BL; D008855:Microscopy, Electron, Scanning; D009374:Neoplasms, Experimental / Q000556:secondary*; D015539:Platelet Activation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011651:Pulmonary Artery / Q000187:drug effects; D011799:Quinazolines / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D010975:Platelet Aggregation Inhibitors; D011799:Quinazolines; C049662:1,5-dihydro-7-(1-piperidinyl)-imidazo(2,1-b)quinazolin-2(3H)-one; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D002118:Calcium