THYROID CARCINOMA INHIBITION BY SOMATOSTATIN

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Disseminated thyroid epithelial carcinoma, unresponsive to surgery and radioiodine, is a fatal disease without known effective therapies. We hypothesize that somatostatin (SRIF) and its analogs can inhibit the growth of human thyroid carcinoma cells and that this action is mediated through activation of specific subtypes of SRIF receptors in these cells. Our preliminary studies demonstrate the presence of saturable, high- affinity SRIF receptors in the cell membranes of several human thyroid epithelial carcinoma cell lines, as well as in surgical samples of human thyroid carcinoma. We have shown that growth of monolayer cultures of these cells is suppressed by SRIF analogs, and pilot studies of human thyroid carcinoma xenografts in a thymic mice have suggested an antiproliferative effect of SRIF analogs. We propose to characterize the expression of SRIF receptor subtypes in eight human thyroid carcinomas. We will use Northern blot analysis of mRNA extracted from these cells and hybridized to specific cDNA probes for each of four different human SRIF receptors. SRIF receptor expression will be quantified by Scatchard analysis of specific radioligand binding to membrane preparations of these cells and surgical tumor samples. The relative expression of SRIF receptor subtypes in thyroid carcinoma cells will be correlated with the ability of different SRIF analogs to suppress cell proliferation in vitro in monolayer and tumor-spheroid cultures, as well as in vivo in athymic mouse Xenografts. These studies should provide a basic for SRIF receptor analysis of tumor samples in order to predict clinical response to SRIF analog therapy. This would provide a foundation for future clinical trials of SRIF analogs to treat thyroid carcinoma in human patients.