Inhibition of tumor cell metastasis by modulation of the vascular prostacyclin/thromboxane A2 system.
The interaction between metastasizing tumor cells and the hemostatic system of the host has been implicated in successful tumor cell dissemination. Prostacyclin (PGI2) decreases metastasis from tail vein injected B16 amelanotic melanoma (B16a) cells when administered 15 min prior to tumor cells. This effect is potentiated by a phosphodiesterase inhibitor. Initial trapping of 125I Udr labelled tumor cells in pulmonary vascular beds is unaltered by PGI2 but retention time is decreased. PGI2 decreases retention time even when administered 60 min post tumor cells. Structurally unrelated thromboxane (TX) synthetase inhibitors and a TXA2 receptor antagonist also reduce metastasis from tail vein injected B16a cells. Furthermore, one inhibitor, 1-(7-carboxyheptyl)imidazole, when injected intraperitoneally reduced spontaneous metastasis from subcutaneous B16a and Lewis lung carcinoma tumors. These results suggest that selective manipulation of PGI2 and TXA2 can reduce the hematogenous spread of tumor cells.
D015121:6-Ketoprostaglandin F1 alpha / Q000494:pharmacology; D000818:Animals; D002277:Carcinoma / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D011464:Epoprostenol / Q000494:pharmacology / Q000502:physiology*; D005260:Female; D007093:Imidazoles / Q000494:pharmacology; D008175:Lung Neoplasms / Q000503:physiopathology; D008297:Male; D008545:Melanoma / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009362:Neoplasm Metastasis / Q000503:physiopathology*; D009366:Neoplasm Seeding; D011247:Pregnancy; D011982:Receptors, Prostaglandin / Q000494:pharmacology; D017482:Receptors, Thromboxane; D013806:Theophylline / Q000494:pharmacology; D013928:Thromboxane A2 / Q000494:pharmacology / Q000502:physiology*; D013930:Thromboxane-A Synthase / Q000494:pharmacology
D007093:Imidazoles; D011982:Receptors, Prostaglandin; D017482:Receptors, Thromboxane; D013928:Thromboxane A2; D015121:6-Ketoprostaglandin F1 alpha; C031572:1-carboxyheptylimidazole; D013806:Theophylline; D011464:Epoprostenol; D013930:Thromboxane-A Synthase