Release of serotonin from human carcinoid tumor cells in vitro and grown in the anterior eye chamber of the rat.

Abstract

Serotonin (5-HT)-producing human carcinoid tumors have been successfully transplanted to the anterior eye chamber of cyclosporine treated rats. Tumor transplants were rapidly vascularized and viable tumor cells could be demonstrated in transplants grown for 2 to 3 weeks in oculo. The release of 5-HT from carcinoid tumor cells grown in the anterior eye chamber and from tumor cells in suspension was studied after stimulation with various adrenoceptor agonists. A dose dependent release of 5-HT upon stimulation with isoprenaline was demonstrated for all viable carcinoid tumors in oculo. The isoprenaline-stimulated release of 5-HT from the tumor cells was further studied in vitro, and was efficiently antagonized by propranolol or nadolol, but not by phenoxybenzamine, indicating activation of beta-adrenoceptors on carcinoid tumor cells upon isoprenaline stimulation. Incubation of tumor cells with verapamil, a calcium channel inhibitor, also prevented the release of 5-HT upon isoprenaline stimulation. Thus, carcinoid tumors can be successfully transplanted to the anterior eye chamber of cyclosporine treated rats, offering new possibilities to study the pharmacologic and biologic features of this tumor. In the future, carcinoid tumors, as well as other endocrine tumors, may be grown in oculo in rats and receptor pharmacology and individual sensitivity to cytotoxic drugs can be studied, thus enabling optimal clinical treatment.